The
Hypothalamus is a portion of the
brainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
that contains a number of small
nucleiIn neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
with a variety of functions. One of the most important functions of the hypothalamus is to link the
nervous systemThe nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
to the
endocrine systemIn physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
via the
pituitary glandIn vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
(hypophysis).
The hypothalamus is located below the
thalamusThe thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, just above the
brain stemIn vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
. In the terminology of
neuroanatomyNeuroanatomy is the study of the anatomy and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems, and thus we can begin to speak of...
, it forms the ventral part of the
diencephalonThe diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
. All
vertebrateVertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
brains contain a hypothalamus. In humans, it is roughly the size of an almond.
The hypothalamus is responsible for certain metabolic processes and other activities of the
autonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
. It synthesizes and secretes certain
neurohormoneA neurohormone is any hormone produced and released by neurons.Examples include:*Thyrotropin-releasing hormone *Gonadotropin-releasing hormone *Adrenocorticotropin-releasing hormone*Oxytocin*Antidiuretic hormone *Epinephrine...
s, often called
hypothalamic-releasing hormonesA releasing hormone or releasing factor is a hormone whose main purpose is to control the release of another hormone. The main releasing hormones secreted by the hypothalamus are:*Thyrotropin-releasing hormone ,...
, and these in turn stimulate or inhibit the secretion of pituitary hormones.
The hypothalamus controls body temperature,
hungerHunger is a sensation experienced when one is required to eat food. In contrast Satiety is the absence of hunger; it is the sensation of feeling full. Appetite is another sensation experienced with eating, however, it differs from hunger; it is the desire to eat food without a physiological need...
,
thirstThirst is the craving for fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids and/or an increase in the concentration of certain osmolites, such as salt...
, fatigue,
sleepSleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
, and
circadian cyclesA circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
.
Structure and Inputs
The hypothalamus is a brain structure composed of distinct nuclei and less anatomically distinct areas. It is found in all vertebrate nervous systems. In mammals, the axons of
magnocellular neurosecretory cellMagnocellular neurosecretory cells are large cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest one being the nucleus circularis...
s of the
paraventricular nucleusThe paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
and the supraoptic nucleus, which contain
oxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
and
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(also called antidiuretic hormone), comprise the
posterior pituitaryThe posterior pituitary comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior...
.
ParvocellularParvocellular can refer to:* Parvocellular cell, located in the lateral geniculate nucleus* Parvocellular pathway of the visual system* Parvocellular neurosecretory cell* Parvocellular red nucleus* Parvocellular reticular nucleus...
neurons of the
paraventricular nucleusThe paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
contain neurons that release
corticotropin-releasing hormoneCorticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
and other hormones into the
hypophyseal portal systemThe hypophyseal portal system is the system of blood vessels that link the hypothalamus and the anterior pituitary in the brain.It allows endocrine communication between the two structures. It is part of the hypothalamic-pituitary-adrenal axis. The anterior pituitary receives releasing and...
where these hormones diffuse to the
anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
.
The hypothalamus coordinates many hormonal and behavioural circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms, and important behaviours. The hypothalamus must therefore respond to many different signals, some of which are generated externally and some internally. The hypothalamus is thus richly connected with many parts of the
central nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, including the brainstem
reticular formationThe reticular formation is a part of the brain that is involved in actions such as awaking/sleeping cycle, and filtering incoming stimuli to discriminate irrelevant background stimuli...
and
autonomicThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
zones, the limbic forebrain (particularly the
amygdalaThe ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
,
septumIn anatomy, a septum is a wall, dividing a cavity or structure into smaller ones.-In human anatomy:...
,
diagonal band of BrocaThe diagonal band of Broca forms the medial margin of the anterior perforated substance.-Contents:It consists of fibers that are said to arise in the parolfactory area, the gyrus subcallosus and the anterior perforated substance, and course backward in the longitudinal striae to the dentate gyrus...
, and the
olfactory bulbThe olfactory bulb is a structure of the vertebrate forebrain involved in olfaction, the perception of odors.-Anatomy:In most vertebrates, the olfactory bulb is the most rostral part of the brain. In humans, however, the olfactory bulb is on the inferior side of the brain...
s, and the
cerebral cortexThe cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
).
The hypothalamus is responsive to:
- Light: daylength and photoperiod for regulating circadian and seasonal rhythms
- Olfactory stimuli, including pheromones
- Steroids, including gonadal steroids and corticosteroids
- Neurally transmitted information arising in particular from the heart, the stomach, and the reproductive tract
- Autonomic
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
inputs
- Blood-borne stimuli, including leptin
Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
, ghrelinGhrelin is a 28 amino acid peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone...
, angiotensinAngiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...
, insulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, pituitary hormones, cytokines, plasma concentrations of glucose and osmolarity etc.
- Stress
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
- Invading microorganisms by increasing body temperature, resetting the body's thermostat upward.
Olfactory stimuli
Olfactory stimuli are important for sex and neuroendocrine function in many species. For instance if a pregnant mouse is exposed to the urine of a 'strange' male during a critical period after coitus then the pregnancy fails (the
Bruce effectThe Bruce effect, or pregnancy block, refers to the tendency for female rodents to terminate their pregnancies following exposure to the scent of an unfamiliar male. The effect has primarily been studied in laboratory mice , but is also observed in deer-mice, meadow voles, and collared lemmings...
). Thus during coitus, a female mouse forms a precise 'olfactory memory' of her partner which persists for several days.
Pheromonal cues aid synchronisation of oestrus in many species; in women, synchronised
menstruationMenstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
may also arise from pheromonal cues, although the role of pheromones in humans is doubted by many .
Blood-borne stimuli
PeptidePeptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
hormones have important influences upon the hypothalamus, and to do so they must evade the
blood-brain barrierThe blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. The hypothalamus is bounded in part by specialized brain regions that lack an effective blood-brain barrier; the capillary
endotheliumThe endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
at these sites is fenestrated to allow free passage of even large proteins and other molecules. Some of these sites are the sites of neurosecretion - the neurohypophysis and the
median eminenceThe median eminence is part of the inferior boundary for the hypothalamus part of the human brain. A small swelling on the tuber cinereum posterior to the infundibulum - atop the pituitary stalk - the median eminence lies in the area roughly bounded on its posterolateral region by the cerebral...
. However others are sites at which the brain samples the composition of the blood. Two of these sites, the SFO (
subfornical organThe subfornical organ, situated on the ventral surface of the fornix, at the interventricular foramina , is one of the circumventricular organs of the brain.-Relations with other circumventricular organs:...
) and the OVLT (
organum vasculosum of the lamina terminalisThe organum vasculosum of the lamina terminalis is one of the circumventricular organs of the brain. Other circumventricular organs are the subfornical organ and the area postrema in the brainstem.-AV3V region:...
) are so-called
circumventricular organsCircumventricular organs are so named because they are positioned at distinct sites around the margin of the ventricular system of the brain.They are among the few sites in the brain which have an incomplete blood–brain barrier...
, where neurons are in intimate contact with both blood and
CSFCerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
. These structures are densely vascularized, and contain osmoreceptive and sodium-receptive neurons which control
drinkingDrinking is the act of consuming water or a beverage through the mouth. Water is required for many of life’s physiological processes. Both excessive and inadequate water intake are associated with health problems.-Physiology:...
,
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
release, sodium excretion, and sodium appetite. They also contain neurons with receptors for
angiotensinAngiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...
, atrial natriuretic factor,
endothelinEndothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....
and
relaxinRelaxin is a protein hormone first described in 1926 by Frederick Hisaw.The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1 , 2 and 3 , and the insulin-like peptides, INSL3, INSL4, INSL5 and INSL6...
, each of which is important in the regulation of fluid and electrolyte balance. Neurons in the OVLT and SFO project to the
supraoptic nucleusThe supraoptic nucleus is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm...
and
paraventricular nucleusThe paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
, and also to preoptic hypothalamic areas. The circumventricular organs may also be the site of action of interleukins to elicit both fever and ACTH secretion, via effects on paraventricular neurons.
It is not clear how all peptides that influence hypothalamic activity gain the necessary access. In the case of
prolactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
and
leptinLeptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
, there is evidence of active uptake at the
choroid plexusThe choroid plexus is a structure in the ventricles of the brain where cerebrospinal fluid is produced...
from blood into CSF. Some pituitary hormones have a negative feedback influence upon hypothalamic secretion; for example,
growth hormoneGrowth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
feeds back on the hypothalamus, but how it enters the brain is not clear. There is also evidence for central actions of
prolactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
.
Findings have suggested that
thyroid hormoneThe thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
(T4) is taken up by the hypothalamic glial cells in the infundibular nucleus/
median eminenceThe median eminence is part of the inferior boundary for the hypothalamus part of the human brain. A small swelling on the tuber cinereum posterior to the infundibulum - atop the pituitary stalk - the median eminence lies in the area roughly bounded on its posterolateral region by the cerebral...
, and that it is here converted into
T3T3 or T-3 may refer to:* SPARC_T3, a CPU introduced by Sun Microsystems in 2010* Digital Signal 3 or T3 line, a type of telecommunications service* Fletcher's Ice Island or T-3, an iceberg discovered by U.S. Air Force Colonel Joseph O...
by the type 2 deiodinase (D2). Subsequently, T3 is transported into the
thyrotropin-releasing hormoneThyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...
(TRH) producing neurons in the
paraventricular nucleusThe paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
. There has been found thyroid hormone receptors in these neurons, indicating that they are indeed sensitive to T3 stimuli. Additionally these neurons expressed
MCT8Monocarboxylate transporter 8 is a protein that in humans is encoded by the SLC16A2 gene.- Function :MCT8 transports a variety of iodo-thyronines including the thyroid hormones T3 and T4.- Clinical significance :...
, a
thyroid hormoneThe thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
transporter, supporting the theory that T3 is transported into them. T3 could then bind to the thyroid hormone receptor in these neurons, and affect the production of thyrotropin-releasing hormone, and thereby regulating thyroid hormone production.
The hypothalamus functions as a type of
thermostatA thermostat is the component of a control system which regulates the temperature of a system so that the system's temperature is maintained near a desired setpoint temperature. The thermostat does this by switching heating or cooling devices on or off, or regulating the flow of a heat transfer...
for the body. It sets a desired body temperature, and stimulates either heat production and retention to raise the blood temperature to a higher setting, or sweating and
vasodilationVasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
to cool the blood to a lower temperature. All
feverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
s result from a raised setting in the hypothalamus; elevated body temperatures due to any other cause are classified as
hyperthermiaHyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
. Rarely, direct damage to the hypothalamus, such as from a
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, will cause a fever; this is sometimes called a
hypothalamic fever. However, it is more common for such damage to cause abnormally low body temperatures.
Steroids
The hypothalamus contains neurons that react strongly to steroids and glucocorticoids – (the steroid hormones of the
adrenal glandIn mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
, released in response to ACTH). It also contains specialized glucose-sensitive neurons (in the
arcuate nucleusThe arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
and ventromedial hypothalamus), which are important for
appetiteThe appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...
. The preoptic area contains thermosensitive neurons; these are important for TRH secretion.
Neural inputs
The hypothalamus receives many inputs from the brainstem; notably from the nucleus of the solitary tract, the locus coeruleus, and the ventrolateral medulla.
OxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
secretion in response to suckling or vagino-cervical stimulation is mediated by some of these pathways;
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
secretion in response to cardiovascular stimuli arising from chemoreceptors in the
carotid bodyThe carotid body is a small cluster of chemoreceptors and supporting cells located near the fork of the carotid artery ....
and
aortic archThe arch of the aorta or the transverse aortic arch is the part of the aorta that begins at the level of the upper border of the second sternocostal articulation of the right side, and runs at first upward, backward, and to the left in front of the trachea; it is then directed backward on the left...
, and from low-pressure
atrial volume receptorsAtrial volume receptors are low pressure baroreceptors that are found in the atria of heart.When these receptors detect pressure drop in the atria, which is indicative for a decrease in blood volume, signal is transmitted from the atrial volume receptors to the hypothalamus of brain. The...
, is mediated by others. In the rat, stimulation of the
vaginaThe vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
also causes
prolactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
secretion, and this results in pseudo-pregnancy following an infertile mating. In the rabbit, coitus elicits reflex
ovulationOvulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
. In the sheep, cervical stimulation in the presence of high levels of estrogen can induce maternal behavior in a virgin ewe. These effects are all mediated by the hypothalamus, and the information is carried mainly by spinal pathways that relay in the brainstem. Stimulation of the nipples stimulates release of oxytocin and prolactin and suppresses the release of
LHLuteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
and
FSHFollicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
.
Cardiovascular stimuli are carried by the
vagus nerveThe vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
, but the vagus also conveys a variety of visceral information, including for instance signals arising from gastric distension to suppress feeding. Again this information reaches the hypothalamus via relays in the brainstem.
In addition hypothalamic function is responsive to --and regulated by-- levels of all three classical monoamine neurotransmitters, i.e. noradrenaline,
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and 5-hydroxytryptamine (serotonin), in those tracts from which it receives enervation. For example noradrenergic inputs arising from the locus coeruleus have important regulatory effects upon CRH levels.
Nuclei
A cross section of the monkey hypothalamus displays 2 of the major hypothalamic nuclei on either side of the fluid-filled 3rd ventricle
The hypothalamic nuclei include the following:
| Region |
Area |
Nucleus |
Function |
| Anterior |
Medial |
Medial preoptic nucleus |
- Regulates the release of gonadotropic hormones from the adenohypophysis
- Contains the sexually dimorphic nucleus
Sexually dimorphic nucleus is a cluster of cells located in the preoptic area of hypothalamus of the brain that is believed to be related to sexual behavior in animals. The volume of SDN is significantly larger in males than in females, caused mainly by greater cell number and larger cell size,...
, which releases GnRH, differential development between sexes is based upon in utero testosterone levels |
| Supraoptic nucleus The supraoptic nucleus is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm...
(SO) |
oxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
release
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
release |
| Paraventricular nucleus The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
* (PV) |
corticotropin-releasing hormone Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
release
oxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
release
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
release |
| Anterior hypothalamic nucleus The anterior hypothalamic nucleus is a nucleus of the hypothalamus.Its function is thermoregulation of the body.The anterior hypothalamus plays a role in regulating sleep....
(AH) |
thermoregulationThermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different...
panting
sweatingPerspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
thyrotropin inhibition |
Suprachiasmatic nucleusThe suprachiasmatic nucleus or nuclei, abbreviated SCN, is a tiny region on the brain's midline, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms...
(SC) |
vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
release
Circadian rhythms |
| Lateral |
Lateral preoptic nucleus |
|
| Lateral nucleus (LT) |
thirstThirst is the craving for fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids and/or an increase in the concentration of certain osmolites, such as salt...
and hungerHunger is the most commonly used term to describe the social condition of people who frequently experience the physical sensation of desiring food.-Malnutrition, famine, starvation:...
|
| Part of supraoptic nucleus (SO) |
vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
release |
| Tuberal |
Medial |
Dorsomedial hypothalamic nucleus The Dorsomedial hypothalamic nucleus is a nucleus of the hypothalamus. It is involved in feeding, drinking, and body weight regulation....
(DM) |
Blood PressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
Heart RateHeart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
GIThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
stimulation |
| Ventromedial nucleus The ventromedial nucleus is a nucleus of the hypothalamus.-Division:It has four subdivisions:* anterior * dorsomedial * ventrolateral * central ....
(VM) |
satiety
neuroendocrine control |
| Arcuate nucleus The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
(AR) |
Growth hormone-releasing hormone (GHRH)
feeding Feeding is the process by which organisms, typically animals, obtain food. Terminology often uses either the suffix -vore from Latin vorare, meaning 'to devour', or phagy, from Greek φαγειν, meaning 'to eat'.-Evolutionary history:...
Dopamine |
| Lateral |
Lateral nucleus (LT) |
thirstThirst is the craving for fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids and/or an increase in the concentration of certain osmolites, such as salt...
and hungerHunger is the most commonly used term to describe the social condition of people who frequently experience the physical sensation of desiring food.-Malnutrition, famine, starvation:...
|
| Lateral tuberal nuclei |
|
| Posterior |
Medial |
Mammillary nuclei (part of mammillary bodies The mammillary bodies are a pair of small round bodies, located on the undersurface of the brain, that, as part of the diencephalon form part of the limbic system. They are located at the ends of the anterior arches of the fornix...
) (MB) |
memory In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
|
| Posterior nucleus The posterior nucleus of the hypothalamus is one of the many nuclei that make up the hypothalamic region of the brain.Its function is thermoregulation of the body.Damage or destruction of this nucleus causes hypothermia...
(PN) |
Increase blood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
pupilThe pupil is a hole located in the center of the iris of the eye that allows light to enter the retina. It appears black because most of the light entering the pupil is absorbed by the tissues inside the eye. In humans the pupil is round, but other species, such as some cats, have slit pupils. In...
lary dilation
shiveringShivering is a bodily function in response to early hypothermia in warm-blooded animals. When the core body temperature drops, the shivering reflex is triggered to maintain homeostasis. Muscle groups around the vital organs begin to shake in small movements in an attempt to create warmth by...
|
| Lateral |
Lateral nucleus (LT) |
- - Note: Paraventricular nucleus is not to be confused with periventricular nucleus
The Periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. Functions in analgesia....
.
See also: ventrolateral preoptic nucleusThe ventrolateral preoptic nucleus is a group of neurons in the hypothalamus. They are primarily active during Non-rapid eye movement sleep, and inhibit other neurons that are involved in wakefulness...
,
periventricular nucleusThe Periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. Functions in analgesia....
.
Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction:
[?? - citation not only needed, but desired].
Outputs
The outputs of the hypothalamus can be divided into two categories: neural projections, and endocrine hormones.
Neural projections
Most fiber systems of the hypothalamus run in two ways (bidirectional).
- Projections to areas caudal
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
to the hypothalamus go through the medial forebrain bundleThe Medial forebrain bundle , is a complex bundle of axons coming from the basal olfactory regions, the periamygdaloid region, and the septal nuclei.-Anatomy:...
, the mammillotegmental tract and the dorsal longitudinal fasciculusThe dorsal longitudinal fasciculus is a white matter fiber tract located within the brain stem, specifically in the dorsal brainstem tegmentum. The DLF travels through the periaqueductal gray matter...
.
- Projections to areas rostral to the hypothalamus are carried by the mammillothalamic tract
The mammillothalamic fasciculus arises from cells in both the medial and lateral nuclei of the mammillary body and by fibers that are directly continued from the fornix.The Mammillothalamic fasciculus then connects the mammillary body to the dorsal tegmental nuclei, the ventral...
, the fornix and terminal striaThe stria terminalis is a structure in the brain consisting of a band of fibers running along the lateral margin of the ventricular surface of the thalamus...
.
- Projections to areas of the sympathetic motor system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
(lateral hornIn the thoracic region, the postero-lateral part of the anterior column projects lateralward as a triangular field, which is named the lateral column .-Nerve Cells in the Lateral Column:...
spinal segments T1-L2/L3 of the) are carried by the hypothalamospinal tractThe hypothalamospinal tract connects the thalamus to the ciliospinal center of the intermediolateral cell column in the spinal cord . It is found in the dorsolateral quadrant of the lateral funiculus, in the lateral tegmentum of the medulla, pons and midbrain. Lesions of the hypothalamospinal tract...
and they activate the sympathetic motor pathway
Endocrine hormones
The hypothalamus affects the endocrine system and governs emotional behavior, such as anger and sexual activity. Most of the hypothalamic hormones generated are distributed to the pituitary via the
hypophyseal portal systemThe hypophyseal portal system is the system of blood vessels that link the hypothalamus and the anterior pituitary in the brain.It allows endocrine communication between the two structures. It is part of the hypothalamic-pituitary-adrenal axis. The anterior pituitary receives releasing and...
. The hypothalamus maintains homeostasis; this includes a regulation of blood pressure, heart rate, and temperature.
| Secreted hormone | | Abbreviation | | Produced by | Effect |
Thyrotropin-releasing hormoneThyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...
(Prolactin-releasing hormone) |
TRH, TRF, or PRH |
Parvocellular neurosecretory neurons |
Stimulate thyroid-stimulating hormone (TSH) Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
(primarily)
Stimulate prolactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
|
DopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
(Prolactin-inhibiting hormone) |
DA or PIH |
Dopamine neurons of the arcuate nucleus The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
|
Inhibit prolactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
|
| Growth hormone-releasing hormone |
GHRH |
Neuroendocrine neurons of the Arcuate nucleus The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
|
Stimulate Growth hormone (GH)Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
|
SomatostatinSomatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
(growth hormone-inhibiting hormone) |
SS, GHIH, or SRIF |
Neuroendocrine cells of the Periventricular nucleus The Periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. Functions in analgesia....
|
Inhibit Growth hormone (GH)Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
Inhibit thyroid-stimulating hormone (TSH)Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
|
| Gonadotropin-releasing hormone Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
|
GnRH or LHRH |
Neuroendocrine cells of the Preoptic area The preoptic area is a region of the hypothalamus. According to the MeSH classification, it is considered part of the anterior hypothalamus. There are four nuclei in this region, according to Terminologia Anatomica .-Functions:The preoptic area is responsible for thermoregulation and receives...
|
Stimulate follicle-stimulating hormone (FSH) Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
Stimulate luteinizing hormone (LH)Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
|
| Corticotropin-releasing hormone Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
|
CRH or CRF |
Parvocellular neurosecretory neurons |
Stimulate adrenocorticotropic hormone (ACTH)Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
release from anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
|
OxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
|
|
Magnocellular neurosecretory cell Magnocellular neurosecretory cells are large cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest one being the nucleus circularis...
s |
Uterine contraction
Lactation (letdown reflex) |
| Vasopressin Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(antidiuretic hormone) |
ADH or AVP |
Magnocellular neurosecretory neurons |
Increase in the permeability to water of the cells of distal tubule and collecting duct in the kidney and thus allows water reabsorption and excretion of concentrated urine |
Control of food intake
The extreme
lateralStandard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
part of the
ventromedial nucleusThe ventromedial nucleus is a nucleus of the hypothalamus.-Division:It has four subdivisions:* anterior * dorsomedial * ventrolateral * central ....
of the hypothalamus is responsible for the control of
foodFood is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals...
intake. Stimulation of this area causes increased food intake. Bilateral
lesionA lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
of this area causes complete cessation of food intake. Medial parts of the nucleus have a controlling effect on the lateral part. Bilateral lesion of the medial part of the ventromedial nucleus causes hyperphagia and obesity of the animal. Further lesion of the lateral part of the ventromedial nucleus in the same animal produces complete cessation of food intake.
There are different hypotheses related to this regulation:
- Lipostatic hypothesis - this hypothesis holds that adipose tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
produces a humoralThe Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...
signal that is proportionate to the amount of fat and acts on the hypothalamus to decrease food intake and increase energy output. It has been evident that a hormoneA hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
leptinLeptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
acts on the hypothalamus to decrease food intake and increase energy output.
- Gutpeptide hypothesis - gastrointestinal
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
hormones like Grp, glucagonGlucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
s, CCKCholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
and others claimed to inhibit food intake. The food entering the gastrointestinal tract triggers the release of these hormones which acts on the brain to produce satiety. The brain contains both CCK-A and CCK-B receptors.
- Glucostatic hypothesis - the activity of the satiety center in the ventromedial nuclei is probably governed by the glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
utilization in the neurons. It has been postulated that when their glucose utilization is low and consequently when the arteriovenous blood glucose difference across them is low, the activity across the neurons decrease. Under these conditions, the activity of the feeding center is unchecked and the individual feels hungry. Food intake is rapidly increased by intraventricular administration of 2-deoxyglucose2-Deoxy-D-glucose is a glucose molecule which has the 2-hydroxyl group replaced by hydrogen, so that it cannot undergo further glycolysis. Glucose hexokinase traps this substance in most cells so that it makes a good marker for tissue glucose use and hexokinase activity. Many cancers have elevated...
therefore decreasing glucose utilization in cells.
- Thermostatic hypothesis - according to this hypothesis, a decrease in body temperature below a given set point stimulates appetite, while an increase above the set point inhibits appetite.
Sexual dimorphism
Several hypothalamic nuclei are sexually dimorphic, i.e. there are clear differences in both structure and function between males and females.
Some differences are apparent even in gross neuroanatomy: most notable is the
sexually dimorphic nucleusSexually dimorphic nucleus is a cluster of cells located in the preoptic area of hypothalamus of the brain that is believed to be related to sexual behavior in animals. The volume of SDN is significantly larger in males than in females, caused mainly by greater cell number and larger cell size,...
within the
preoptic areaThe preoptic area is a region of the hypothalamus. According to the MeSH classification, it is considered part of the anterior hypothalamus. There are four nuclei in this region, according to Terminologia Anatomica .-Functions:The preoptic area is responsible for thermoregulation and receives...
. However most of the differences are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons.
The importance of these changes can be recognised by functional differences between males and females. For instance, males of most species prefer the odor and appearance of females over males, which is instrumental in stimulating male sexual behavior. If the sexually dimorphic nucleus is lesioned, this preference for females by males diminishes. Also, the pattern of secretion of
growth hormoneGrowth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
is sexually dimorphic, and this is one reason why in many species, adult males are much larger than females.
Responses to ovarian steroids
Other striking functional dimorphisms are in the behavioral responses to ovarian steroids of the adult. Males and females respond differently to ovarian steroids, partly because the expression of estrogen-sensitive neurons in the hypothalamus is sexually dimorphic, i.e. estrogen receptors are expressed in different sets of neurons.
EstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
and
progesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
can influence gene expression in particular neurons or induce changes in
cell membraneThe cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
potential and
kinaseIn chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
activation, leading to diverse non-genomic cellular functions. Estrogen and progesterone bind to their cognate nuclear hormone receptors, which translocate to the cell nucleus and interact with regions of DNA known as
hormone response elementA hormone response element is a response element for hormones, a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription...
s (HREs) or get tethered to another
transcription factorIn molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
's binding site.
Estrogen receptorEstrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
(ER) has been shown to transactivate other transcription factors in this manner, despite the absence of an estrogen response element (ERE) in the proximal promoter region of the gene. ERs and
progesterone receptorThe progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
s (PRs) are generally gene activators, with increased mRNA and subsequent protein synthesis following hormone exposure.
Male and female brains differ in the distribution of estrogen receptors, and this difference is an irreversible consequence of neonatal steroid exposure. Estrogen receptors (and progesterone receptors) are found mainly in neurons in the anterior and mediobasal hypothalamus, notably:
- the preoptic area (where LHRH neurons are located)
- the periventricular nucleus (where somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
neurons are located)
- the ventromedial hypothalamus (which is important for sexual behavior).
Gonadal steroids in neonatal life of rats
In neonatal life, gonadal steroids influence the development of the neuroendocrine hypothalamus. For instance, they determine the ability of females to exhibit a normal reproductive cycle, and of males and females to display appropriate reproductive behaviors in adult life.
- If a female rat is injected once with testosterone in the first few days of postnatal life (during the "critical period" of sex-steroid influence), the hypothalamus is irreversibly masculinized; the adult rat will be incapable of generating an LH surge in response to estrogen (a characteristic of females), but will be capable of exhibiting male sexual behaviors (mounting a sexually receptive female).
- By contrast, a male rat castrated just after birth will be feminized, and the adult will show female sexual behavior in response to estrogen (sexual receptivity, lordosis behavior
Lordosis behavior, or mammalian lordosis, is a sexual response in mammals, such as mice and cats, that consists of a ventral arching of the spine. During lordosis, the spine curves so that the apex points in the ventral direction. That is, the spine arches inward toward the abdomen.Lordosis aids in...
).
Androgens in primates
In primates, the developmental influence of androgens is less clear, and the consequences are less understood. Within the brain, testosterone is aromatized to (
estradiolEstradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
), which is the principal active hormone for developmental influences. The human testis secretes high levels of testosterone from about week 8 of fetal life until 5–6 months after birth (a similar perinatal surge in testosterone is observed in many species), a process that appears to underlie the male phenotype. Estrogen from the maternal circulation is relatively ineffective, partly because of the high circulating levels of steroid-binding proteins in pregnancy.
Human sexual orientation and the hypothalamus
According to D.F. Swaab, writing in a July 2008 paper, "Neurobiological research related to sexual orientation in humans is only just gathering momentum, but the evidence already shows that humans have a vast array of brain differences, not only in relation to gender, but also in relation to sexual orientation."
Swaab first reported on the relationship between sexual orientation in males and the hypothalamus's "clock", the
suprachiasmatic nucleus (SCN)The suprachiasmatic nucleus or nuclei, abbreviated SCN, is a tiny region on the brain's midline, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms...
. In 1990, Swaab and Hofman reported that the SCN of heterosexual men was significantly larger than in women, and the SCN of homosexual men was significantly less than in heterosexual men. Then in 1995, Swaab et al. linked brain development to sexual orientation by treating male rats both pre- and postnatally with ATD, an
aromataseAromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
blocker in the brain. This produced an enlarged SCN and bisexual behavior in the adult male rats. In 1991, LeVay showed that part of the sexually dimorphic nucleus (SDN), the interstitial nuclei of the anterior hypothalamus (INAH) 3, is twice as large in heterosexual men as and homosexual women, in terms of volume but not number of neurons.
In 2004 and 2006, two studies by Berglund, Lindström, and Savic used
Positron Emission TomographyPositron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) to observe how the hypothalamus responds to smelling common odors, the scent of testosterone found in male sweat, and the scent of estrogen found in female urine. These studies showed that the hypothalamus of heterosexual men and homosexual women both respond to estrogen. Also, the hypothalamus of homosexual men and heterosexual women both respond to testosterone. The hypothalamus of all four groups did not respond to the common odors, which produced a normal olfactory response in the brain.
Other influences upon hypothalamic development
Sex steroids are not the only important influences upon hypothalamic development; in particular,
pre-pubertalPuberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
stress in early life (of rats) determines the capacity of the adult hypothalamus to respond to an acute stressor. Unlike gonadal steroid receptors,
glucocorticoidGlucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
receptors are very widespread throughout the brain; in the
paraventricular nucleusThe paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
, they mediate negative feedback control of
CRFCorticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
synthesis and secretion, but elsewhere their role is not well understood.
See also
- Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...
(HPA axis)
- Neuroendocrinology
Neuroendocrinology is the study of the extensive interactions between the nervous system and the endocrine system, including the biological features of the cells that participate, and how they functionally communicate...
- John Leonora
John Leonora , is notable for his research into the critical role of hypothalamic "factors" for indirectly controlling the metabolism of such avascular tissues as the dental enamel, the dentin, and the Islands of Langerhans . His contributions have given a radically new perspective to the systemic...
- Incertohypothalamic pathway
The incertohypothalamic pathway is a short dopaminergic pathway in the hypothalamus of the brain. It has a role in sexual behaviour....
Added Reference
de Vries, GJ, and Sodersten P (2009) Sex differences in the brain: the relation between structure and function. Hormones and Behavior 55:589-596.
External links