Luteinizing hormone (
LH, also known as
lutropin) is a
hormoneA hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...
produced by the anterior pituitary gland.
- In the female, an acute rise of LH – the LH surge – triggers ovulation
Ovulation is the process in the females menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum that participates in reproduction...
and corpus luteum development.
- In the male, where LH had also been called Interstitial Cell Stimulating Hormone (ICSH), it stimulates Leydig cell
Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle. They can secrete testosterone and are often closely related to nerves...
production of testosteroneTestosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.In men,...
.
Structure
LH is a heterodimeric
glycoproteinGlycoproteins are proteins that contain oligosaccharide chains covalently attached to their polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
. Each
monomerA monomer is a small molecule that may become chemically bonded to other monomers to form a polymer...
ic unit is a
glycoproteinGlycoproteins are proteins that contain oligosaccharide chains covalently attached to their polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
molecule; one alpha and one beta subunit make the full, functional protein.
Its structure is similar to the other glycoprotein hormones,
follicle-stimulating hormoneFollicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotropes of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH),
thyroid-stimulating hormoneThyroid-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....
(TSH), and
human chorionic gonadotropinHuman chorionic gonadotropin or Human chorionic gonadotrophin is a glycoprotein hormone produced in pregnancy that is made by the developing embryo soon after conception and later by the syncytiotrophoblast...
(hCG). The protein dimer contains 2 glycopeptidic subunits, labeled alpha and beta subunits, that are non-covalently associated (i.e. without any disulfide bridge linking them). :
- The alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino acids in human but 96 amino acids in almost all other vertebrate species (glycoprotein hormones do not exist in invertebrates).
- The beta subunits vary. LH has a beta subunit of 121 amino acids (LHB) that confers its specific biologic action and is responsible for the specificity of the interaction with the LH receptor. This beta subunit contains an amino acid sequence that exhibits large homologies with that of the beta subunit of hCG
Human chorionic gonadotropin or Human chorionic gonadotrophin is a glycoprotein hormone produced in pregnancy that is made by the developing embryo soon after conception and later by the syncytiotrophoblast...
and both stimulate the same receptor, however, the hCG beta subunit contains an additional 24 amino acids, and the two hormones differ in the composition of their sugar moieties.
The different composition of these
oligosaccharideAn oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars. The name is derived from the Greek word oligos, meaning "a few", and from the Latin/Greek word sacchar which means "sugar"...
s affects bioactivity and speed of degradation. The biologic
half-lifeHalf-life is the period of time, for a substance undergoing decay, to decrease by half. The name originally was used to describe a characteristic of unstable atoms , but may apply to any quantity which follows a set-rate decay....
of LH is 20 minutes, shorter than that of FSH (3–4 hours) or hCG (24 hours).
Genes
The
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
for the
alpha subunit is located on chromosome 6q12.21.
The luteinizing hormone
beta subunit gene is localized in the LHB/CGB gene cluster on chromosome 19q13.32. In contrast to the alpha gene activity, beta LH subunit gene activity is restricted to the pituitary gonadotropic cells. It is regulated by the gonadotropin releasing hormone from the
hypothalamusThe hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
. Inhibin, activin, and sex hormones do not affect genetic activity for the beta subunit production of LH.
Activity
In both males and females, LH is essential for reproduction.
- In females, at the time of menstruation, FSH initiates follicular growth, specifically affecting granulosa cell
A granulosa cell is a somatic cell of the sex cord that is closely associated with the developing female gamete in the ovary of mammals.-Anatomy and function:...
s. With the rise in estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
s, LH receptors are also expressed on the maturing follicle that produces an increasing amount of estradiolEstradiol is a sex hormone. Estradiol is the predominant sex hormone present in females; however, it is present in males, albeit at lower levels, as well. It represents the major estrogen in humans...
. Eventually at the time of the maturation of the follicle, the estrogen rise leads via the hypothalamic interface to the “positive feed-back” effect, a release of LH over a 24-48 hour period. This 'LH surge' triggers ovulationOvulation is the process in the females menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum that participates in reproduction...
thereby not only releasing the egg, but also initiating the conversion of the residual follicle into a corpus luteumThe corpus luteum is a temporary endocrine structure in mammals, involved in production of progestogen, which is needed to maintain the endometrium.-Development and structure:...
that, in turn, produces 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...
to prepare the endometrium-Function:The endometrium functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue...
for a possible implantationImplantation is an event that occurs early in pregnancy in which the embryo adheres to the wall of uterus. At this stage of prenatal development, the embryo is a blastocyst...
. LH is necessary to maintain luteal function for the first two weeks. In case of a pregnancyPregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the uterus of a female. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets. Human pregnancy is the most studied of all mammalian pregnancies. Obstetrics is the surgical field...
luteal function will be further maintained by the action of hCG (a hormone very similar to LH) from the newly established pregnancy. LH supports thecal cells in the ovary that provide androgenAndrogen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and...
s and hormonal precursors for estradiol production.
- In the male, LH acts upon the Leydig cells of the testis and is responsible for the production of testosterone
Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.In men,...
, an androgenAndrogen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. This includes the activity of the accessory male sex organs and...
that exerts both endocrine activity and intratesticular activity on spermatogenesisSpermatogenesis is the process by which male spermatogonia develop into mature spermatozoa. Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus, spermatogenesis is the male version of gametogenesis. In mammals it occurs in the male testes and epididymis in a...
.
The release of LH at the pituitary gland is controlled by pulses of
gonadotropin-releasing hormoneGonadotropin-releasing hormone , also known as Luteinizing-hormone releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of FSH and LH from the anterior pituitary...
(GnRH) from the
hypothalamusThe hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
. Those pulses, in turn, are subject to the estrogen feedback from the gonads.
Normal levels
LH levels are normally low during
childhoodChildhood is a broad term usually applied to the phase of development in humans between infancy and adulthood.-Age definition of a child:...
and, in women, high after
menopauseMenopause is the time in a woman’s life when menstruation ends. It is part of a biological process that begins, for most women, in their mid-fifties. During this time, the ovaries gradually produce lower levels of natural sex hormones—estrogen and progesterone...
. As LH is secreted as pulses, it is necessary to follow its concentration over a sufficient period of time to get a proper information about its blood level.
During the reproductive years typical levels are between 5-20 mIU/ml.
Physiologic high LH levels are seen during the LH surge (v.s.); typically they last 48 hours.
Ovulation predictor kit (LH kit)
The detection of the Luteinising hormone surge indicates impending
ovulationOvulation is the process in the females menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum that participates in reproduction...
. LH can be detected by urinary ovulation predictor kits (OPK, also LH-kit) that are performed, typically daily, around the time ovulation may be expected. The conversion from a negative to a positive reading would suggest that ovulation is about to occur within 24–48 hours, giving women two days to engage in
sexual intercourseSexual intercourse, also known as copulation or coitus, commonly refers to the act in which the male reproductive organ enters the female reproductive tract. The two entities may be of opposite sexes or not, or they may be hermaphroditic, as is the case with snails...
or
artificial inseminationArtificial insemination is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse...
with the intentions of conceiving.
Tests may be read manually using a colour-change paper strip, or digitally with the assistance of reading electronics.
Tests for Luteinising hormone may be combined with testing for
estradiolEstradiol is a sex hormone. Estradiol is the predominant sex hormone present in females; however, it is present in males, albeit at lower levels, as well. It represents the major estrogen in humans...
in tests such as the Clearblue
fertility monitorA fertility monitor is a computerized device used for fertility awareness. Some brands are marketed only to assist in pregnancy achievement, while other brands are advertised for both pregnancy achievement and as birth control...
.
The sensitivity of LH tests are measured in milli international unit, with tests commonly available in the range 10-40 m.i.u.
As sperm can stay viable in the woman for several days, LH tests are not recommended for contraceptive practices, as the LH surge typically occurs after the beginning of the fertile window.
[note: photo shows "negative" results, i.e. no LH surge]
Relative elevations
In children with
precocious pubertyPrecocious puberty is an unusually early onset of puberty, the process of sexual maturation triggered by the brain or exogenous chemicals, which usually begins in late childhood and results in reproductive maturity and completion of growth...
of pituitary or central origin, LH and FSH levels may be in the reproductive range instead of the low levels typical for their age.
During the reproductive years, relatively elevated LH is frequently seen in patients with the
polycystic ovary syndromePolycystic ovary syndrome is an endocrine disorder that affects approximately 5% of all women.It occurs amongst all races and nationalities, is the most common hormonal disorder among women of reproductive age, and is a leading cause of infertility.The principal features are obesity, anovulation ,...
; however it would be unusual for them to have LH levels outside of the normal reproductive range.
High LH levels
Persistently high LH levels are indicative of situations where the normal restricting feedback from the gonad is absent, leading to a pituitary production of both LH and FSH. While this is typical in the menopause, it is abnormal in the reproductive years. There it may be a sign of:
- Premature menopause
- Gonadal dysgenesis
Gonadal dysgenesis is a reproductive system development disorder. It is characterizedby a progressive loss of primordial germ cells on the developing gonads of an embryo....
, Turner syndromeTurner syndrome or Ullrich-Turner syndrome encompasses several conditions, of which monosomy X is most common. It is a chromosomal disorder in which all or part of one of the sex chromosomes is absent...
- Castration
Castration is any action, surgical, chemical, or otherwise, by which a male loses the functions of the testicles or a female loses the functions of the ovaries...
- Swyer syndrome
Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be partially non-functional streaks. Estrogen and progesterone therapy is...
- Polycystic Ovary Syndrome
Polycystic ovary syndrome is an endocrine disorder that affects approximately 5% of all women.It occurs amongst all races and nationalities, is the most common hormonal disorder among women of reproductive age, and is a leading cause of infertility.The principal features are obesity, anovulation ,...
- Certain forms of CAH
CAH can stand for:* Congenital adrenal hyperplasia* Calcium Aluminate Hydrate, an important phase in cement chemistry* Crime against humanity* Capital Airports Holding Company, Airport holdings company in the People's Republic of China....
- Testicular failure
Deficient LH activity
Diminished secretion of LH can result in failure of gonadal function (hypogonadism). This condition is typically manifest in males as failure in production of normal numbers of sperm. In females, amenorrhea is commonly observed.
Conditions with very low LH secretions are:
- Kallmann syndrome
Kallmann syndrome is a hypogonadism caused by a deficiency of gonadotropin-releasing hormone , which is created by the hypothalamus...
- Hypothalamic suppression
- Hypopituitarism
Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...
- Eating disorder
An eating disorder is a condition which affects an individuals eating habits, either as a result of their own doing , or as a bodily reaction to the consumption of food. Eating disorders can range from mild mental anguish to life-threatening conditions, and can affect every aspect of an...
- Hyperprolactinemia
- Gonadotropin deficiency
- Gonadal suppression therapy
- GnRH antagonist
- GnRH agonist (downregulation)
Availability
LH is available mixed with FSH in the form of Pergonal, and other forms of urinary gonadotropins . More purified forms of urinary gonadotropins may reduce the LH portion in relation to FSH. Recombinant LH is available as lutropin alfa (Luveris). All these medications have to be given parenterally. They are commonly used in infertility therapy to stimulate follicular development, notably in IVF therapy.
Often, hCG medication is used as an LH substitute because it activates the same receptor. Medically used hCG is derived from urine of pregnant women, less costly, and has a longer half-life than LH.