Endocrinology of reproduction
Encyclopedia
Hormonal regulation occurs at every stage of development. A milieu of hormones simultaneously affects development of the fetus
during embryogenesis
and the mother, perhaps most notably human chorionic gonadotropin
(hCG) and progesterone
(P4).
(hCG), progesterone
, 17β-estradiol, endorphins and gonadotropin-releasing hormone
(GnRH) synthesis are rapidly upregulated by the developing embryo following fertilization of the ovum .
During early embryonic development, paracrine/juxtacrine signaling of hCG induces blastulation and neurulation
. An in vitro model of early human embryogenesis (human embryonic stem cells (hESCs)) has demonstrated that hCG promotes cell proliferation via the LH/hCG receptor (LHCGR). hCG signaling upregulates the expression of steroidogenic acute regulatory protein
(StAR)-mediated cholesterol transport and the synthesis of progesterone in hESC. The production of progesterone at this time induces embryroid body (akin to blastulation) and rosette (akin to neurulation) formation in vitro. Progesterone induces the differentiation of pluripotent hESC to neural precursor cells .
Suppression of P4 signaling following withdrawal of progesterone, or treatment with the progesterone receptor antagonist RU-486 (mifepristone
), inhibits the differentiation of hESC colonies into embryoid bodies (blastulation) or rosettes (neurulation
). RU-486, a drug commonly used to terminate pregnancy in its early stages, acts not only to abort the embryo, but also to inhibit normal embryonic development .
-associated hormones such as hCG and sex steroids regulate numerous biological processes in the maternal system prior to and during pregnancy. The embryo orchestrates biological changes that occur in both the embryo and the mother. The embryo upregulates hCG, drives growth of the cell, and upregulates P4 production driving development. hCG and P4 direct changes in the mother to enable successful pregnancy (see below) via upregulation of specific hormones that act to direct both endocrinological and biological changes within the mother for successful pregnancy.
.
is upregulated by human chorionic gonadotropin and progesterone and downregulated by estrogen. The balance of influences of progesterone and estrogen determine the state of angiogenesis in the uterus during early pregnancy .
regulate lymphocyte
proliferation at the maternal-fetal interface, locally suppressing maternal immune response against the developing embryo .
upon which lobuloalveolar structures form under the influence of prolactin
. Prolactin stimulates lactogenesis .
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
during embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
and the mother, perhaps most notably human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(hCG) and progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
(P4).
Embryogenesis
Human chorionic gonadotropinHuman chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(hCG), progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
, 17β-estradiol, endorphins and gonadotropin-releasing hormone
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) synthesis are rapidly upregulated by the developing embryo following fertilization of the ovum .
During early embryonic development, paracrine/juxtacrine signaling of hCG induces blastulation and neurulation
Neurulation
Neurulation is the stage of organogenesis in vertebrate embryos, during which the neural tube is transformed into the primitive structures that will later develop into the central nervous system....
. An in vitro model of early human embryogenesis (human embryonic stem cells (hESCs)) has demonstrated that hCG promotes cell proliferation via the LH/hCG receptor (LHCGR). hCG signaling upregulates the expression of steroidogenic acute regulatory protein
Steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR , is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones...
(StAR)-mediated cholesterol transport and the synthesis of progesterone in hESC. The production of progesterone at this time induces embryroid body (akin to blastulation) and rosette (akin to neurulation) formation in vitro. Progesterone induces the differentiation of pluripotent hESC to neural precursor cells .
Suppression of P4 signaling following withdrawal of progesterone, or treatment with the progesterone receptor antagonist RU-486 (mifepristone
Mifepristone
Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-38486 or simply RU-486, its...
), inhibits the differentiation of hESC colonies into embryoid bodies (blastulation) or rosettes (neurulation
Neurulation
Neurulation is the stage of organogenesis in vertebrate embryos, during which the neural tube is transformed into the primitive structures that will later develop into the central nervous system....
). RU-486, a drug commonly used to terminate pregnancy in its early stages, acts not only to abort the embryo, but also to inhibit normal embryonic development .
Influence of Maternal Hormones
PregnancyPregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
-associated hormones such as hCG and sex steroids regulate numerous biological processes in the maternal system prior to and during pregnancy. The embryo orchestrates biological changes that occur in both the embryo and the mother. The embryo upregulates hCG, drives growth of the cell, and upregulates P4 production driving development. hCG and P4 direct changes in the mother to enable successful pregnancy (see below) via upregulation of specific hormones that act to direct both endocrinological and biological changes within the mother for successful pregnancy.
Maintenance of the endometrial lining
The early embryo has 1–2 weeks in order to produce sufficient hCG in order to stabilize the endometrial lining to allow for blastocyst attachment. The dramatic increase in trophoblastic and corpus luteal hCG synthesis signals both blastocyst and corpus luteal production of P4, crucial for the maintenance of the endometriumEndometrium
-Function:The endometrium is the innermost glandular layer and 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...
.
Attachment and invasion of cytotrophoblast into endometrium
hCG secreted by cytotrophoblastic cells of the blastocyst controls endometrial tissue remodeling by both activation of matrix matalloproteinases (MMP) that control the maternal extracellular matrix and inhibition of tissue-inhibitors of matrix-metalloproteinases (TIMP). hCG mediates invasion and attachment to the endometrium . Low levels of hCG increase risk of pre-eclampsia .Uterine angiogenesis
Uterine angiogenesisAngiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
is upregulated by human chorionic gonadotropin and progesterone and downregulated by estrogen. The balance of influences of progesterone and estrogen determine the state of angiogenesis in the uterus during early pregnancy .
Suppression of the maternal immune system
High levels of progesterone produced by the embryonic placentaPlacenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
regulate lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
proliferation at the maternal-fetal interface, locally suppressing maternal immune response against the developing embryo .
Suppression of GnRH secretion to prevent further follicular maturation
Negative feedback of progesterone inhibits hypothalamic pulsatile GnRH neurosecretion, ovulatory GnRH release and pituitary gonadotropin surges thereby effectively preventing further follicular maturation .Preparation of maternal metabolic systems
Progesterone regulates metabolism of carbohydrates, proteins, and lipids, resulting in physiological changes associated with pregnancy. The mix of hormones characteristic of early pregnancy promote natural growth of maternal tissues and weight gain . In the second half of pregnancy, progesterone and prolactin prepare the mammary glands for lactation .Preparation of mammary glands for lactation
Estrogens and progesterone promote mammary epithelial cell proliferation resulting in the formation of the primary and secondary ductal structure. Progesterone induces formation of tertiary side-branches in the mammary glands during puberty and during the luteal phase of the menstrual cycleMenstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
upon which lobuloalveolar structures form under the influence of prolactin
Prolactin
Prolactin 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...
. Prolactin stimulates lactogenesis .