Hypothalamic-pituitary-gonadal axis
Encyclopedia
The hypothalamic–pituitary–gonadal axis (also HPG axis) refers to the effects of the hypothalamus
, pituitary gland
, and gonad
s as if these individual endocrine glands were a single entity as a whole. Because these glands often behave in cooperation, physiologists
and endocrinologists
find it convenient and descriptive to speak of them as a single system.
The hypothalamic–pituitary–gonadal axis is a critical part in the development and regulation of a number of the body's systems, such as the reproductive and immune systems. Fluctuations in the hormones cause changes in the hormones produced by each gland and have various widespread and local effects on the body.
This axis controls development, reproduction, and aging in animals. The hypothalamus
produces gonadotropin-releasing hormone
(GnRH). The anterior portion of the pituitary gland
produces luteinizing hormone
(LH) and follicle-stimulating hormone
(FSH), and the gonads produce estrogen
and testosterone
.
In oviparous organisms (e.g. fish, reptiles, amphibians, birds), the HPG axis is commonly referred to as the hypothalamus-pituitary-gonadal-liver axis (HPGL-axis) in females. Many egg-yolk and chorionic proteins are synthesized heterologously in the liver, which are necessary for oocyte growth and development. Examples of such necessary liver proteins are vitellogenin
and choriogenin.
is located in the brain and secretes GnRH. GnRH travels down the anterior portion of the pituitary via the hypophyseal portal system
and binds to receptors on the secretory cells of the adenohypophysis. In response to GnRH stimulation these cells produce LH and FSH, which travel into the blood stream.
These two hormones play an important role in communicating to the gonads. In females FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle
and ovarian cycle. Estrogen forms a negative feedback loop by inhibiting the production of GnRH in the hypothalamus. Inhibin acts to inhibit activin, which is a peripherally produced hormone that positively stimulates GnRH producing cells. Follistatin
which is also produced in all body tissue, inhibits activin and gives the rest of the body more control over the axis. In males LH stimulates the interstitial cells located in the testes to produce testosterone, and FSH plays a role in spermatogenesis
. Only small amounts of estrogen are secreted in males. Recent research has shown a neurosteroid axis exists, which help the cortex to regulate the hypothalamus’s production of GnRH.
In males, the production of GnRH, LH, and FSH are similar, but the effects of these hormones are different. FSH stimulates sustentacular cells to release androgen-binding protein, which promotes testosterone
binding. LH binds to the interstitial cells, causing them to secrete testosterone
. Testosterone
is required for normal spermatogenesis and inhibits the hypothalamus. Inhibin is produced by the spermatogenic cells, which also through inactivating activin inhibits the hypothalamus. After puberty these hormones levels remain relatively constant.
the HPG axis is activated by the secretions of estrogen from the ovaries or testosterone
from the testes. This activation of estrogen
and testosterone
causes physiological and psychological changes. Once activated, the HPG axis continues to function in men for the rest of their life but becomes deregulated in women, leading to menopause
. This deregulation is caused mainly by the lack of oocytes that normally produce estrogen to create the positive feedback loop. Over several years, the activity the HPG axis decreases and women are no longer fertile.
Although males remain fertile until death, the activity of the HPG axis decreases. As males age, the testes begin to produce less testosterone
, leading to a condition known as post-pubertal hypogonadism
. The cause of the decreased testosterone
is unclear and a current topic of research. Post-pubertal hypogonadism results in progressive muscle mass decrease, increase in visceral fat mass, loss of libido, impotence, decreased attention, increased risk of fractures, and abnormal sperm production.
and migrate to result in sexual dimorphism
s. These physical differences lead to differences in behavior. While GnRH has not been shown to have any direct influence on regulating brain structure and function, gonadotropins, sex steroids, and activin have been shown to have such effects. It is thought that FSH may have an important role in brain development and differentiation.
Testosterone
levels have been shown to relate to aggression and sex drive. This helps create synaptogenesis by promoting neurite development and migration. Activin promotes neural plasticity throughout the lifespan and regulates the neurotransmitters of peripheral neurons. Environment can also affect hormones and behavior interaction. Women have more connections between areas of language better enabling them to communicate than men. On average men out perform women on spatial reasoning tests, which is theorized to result from sexual differences. Testosterone
has been linked to aggression and sex drive; therefore men tend to be more competitive or aggressive than women. There is also a large amount of individual diversity within all these traits and hormone levels.
For example, in males mutations in the GnRH coding gene could result in hypogonadotrophic hypogonadism. A mutation that cause a gain of function for LH receptor can result in a condition known as testotoxicosis, which cause puberty to occur between ages 2–3 years. Loss of function of LH receptors can cause male pseudohermaphroditism. In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.
. Hormonally based birth control alters the HPG axis by mimicking the pregnancy state. The primary active ingredients are synthetic progesterones, which mimic biologically derived progesterone. The synthetic progesterone prevent the hypothalamus from releasing GnRH and the pituitary from releasing LH and FSH; therefore it prevents the ovarian cycle from entering the menstrual phase and prevents follicle development and ovulation. Also as a result, many of the side effects are similar to the symptoms of pregnancy. Hormone replacement therapy disrupt the HPG axis decline but focus more on estrogen. Alzheimer's has been shown to have a hormonal component, which could possibly be used to a method of prevent the disease.
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, pituitary gland
Pituitary gland
In 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...
, and gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s as if these individual endocrine glands were a single entity as a whole. Because these glands often behave in cooperation, physiologists
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
and endocrinologists
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
find it convenient and descriptive to speak of them as a single system.
The hypothalamic–pituitary–gonadal axis is a critical part in the development and regulation of a number of the body's systems, such as the reproductive and immune systems. Fluctuations in the hormones cause changes in the hormones produced by each gland and have various widespread and local effects on the body.
This axis controls development, reproduction, and aging in animals. The hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
produces 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). The anterior portion of the pituitary gland
Pituitary gland
In 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...
produces luteinizing hormone
Luteinizing hormone
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...
(LH) and follicle-stimulating hormone
Follicle-stimulating hormone
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...
(FSH), and the gonads produce estrogen
Estrogen
Estrogens , 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 testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
.
In oviparous organisms (e.g. fish, reptiles, amphibians, birds), the HPG axis is commonly referred to as the hypothalamus-pituitary-gonadal-liver axis (HPGL-axis) in females. Many egg-yolk and chorionic proteins are synthesized heterologously in the liver, which are necessary for oocyte growth and development. Examples of such necessary liver proteins are vitellogenin
Vitellogenin
Vitellogenin is a synonymous term for the gene and the expressed protein. The protein molecule is classified as a glycolipoprotein, having properties of a sugar, fat and protein...
and choriogenin.
Location and regulation
The hypothalamusHypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
is located in the brain and secretes GnRH. GnRH travels down the anterior portion of the pituitary via the hypophyseal portal system
Hypophyseal portal system
The 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...
and binds to receptors on the secretory cells of the adenohypophysis. In response to GnRH stimulation these cells produce LH and FSH, which travel into the blood stream.
These two hormones play an important role in communicating to the gonads. In females FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle
Menstrual 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....
and ovarian cycle. Estrogen forms a negative feedback loop by inhibiting the production of GnRH in the hypothalamus. Inhibin acts to inhibit activin, which is a peripherally produced hormone that positively stimulates GnRH producing cells. Follistatin
Follistatin
Follistatin also known as activin-binding protein is a protein that in humans is encoded by the FST gene. Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals....
which is also produced in all body tissue, inhibits activin and gives the rest of the body more control over the axis. In males LH stimulates the interstitial cells located in the testes to produce testosterone, and FSH plays a role in spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
. Only small amounts of estrogen are secreted in males. Recent research has shown a neurosteroid axis exists, which help the cortex to regulate the hypothalamus’s production of GnRH.
Reproduction
One of the most important functions of the HPG axis is to regulate reproduction by controlling the uterine and ovarian cycles. In females, the positive feedback loop between estrogen and luteinizing hormone help to prepare the follicle in the ovary and the uterus for ovulation and implantation. When the egg is released, the ovary begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary thus stopping the estrogen-LH positive feedback loop. If conception occurs, the fetus will take over the secretion of progesterone; therefore the mother cannot ovulate again. If conception does not occur, decreasing excretion of progesterone will allow the hypothalamus to restart secretion of GnRH. These hormone levels also control the uterine (menstrual) cycle causing the proliferation phase in preparation for ovulation, the secretory phase after ovulation, and menstruation when conception does not occur. The activation of the HPG axis in both males and females during puberty also causes individuals to acquire secondary sex characteristics.In males, the production of GnRH, LH, and FSH are similar, but the effects of these hormones are different. FSH stimulates sustentacular cells to release androgen-binding protein, which promotes testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
binding. LH binds to the interstitial cells, causing them to secrete testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
. Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
is required for normal spermatogenesis and inhibits the hypothalamus. Inhibin is produced by the spermatogenic cells, which also through inactivating activin inhibits the hypothalamus. After puberty these hormones levels remain relatively constant.
Life cycle
The activation and deactivation of the HPG axis also helps to regulate life cycles. At birth FSH and LH levels are elevated, and females also have a lifetime supply of primary oocytes. These levels decrease and remain low through childhood. During pubertyPuberty
Puberty 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...
the HPG axis is activated by the secretions of estrogen from the ovaries or testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
from the testes. This activation of estrogen
Estrogen
Estrogens , 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 testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
causes physiological and psychological changes. Once activated, the HPG axis continues to function in men for the rest of their life but becomes deregulated in women, leading to menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
. This deregulation is caused mainly by the lack of oocytes that normally produce estrogen to create the positive feedback loop. Over several years, the activity the HPG axis decreases and women are no longer fertile.
Although males remain fertile until death, the activity of the HPG axis decreases. As males age, the testes begin to produce less testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
, leading to a condition known as post-pubertal hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
. The cause of the decreased testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
is unclear and a current topic of research. Post-pubertal hypogonadism results in progressive muscle mass decrease, increase in visceral fat mass, loss of libido, impotence, decreased attention, increased risk of fractures, and abnormal sperm production.
Sexual dimorphism and behavior
Sex steroids also affect behavior, because sex steroids affect our brain structure and functioning. During development, hormones help determine how neurons synapseSynapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
and migrate to result in sexual dimorphism
Sexual dimorphism
Sexual dimorphism is a phenotypic difference between males and females of the same species. Examples of such differences include differences in morphology, ornamentation, and behavior.-Examples:-Ornamentation / coloration:...
s. These physical differences lead to differences in behavior. While GnRH has not been shown to have any direct influence on regulating brain structure and function, gonadotropins, sex steroids, and activin have been shown to have such effects. It is thought that FSH may have an important role in brain development and differentiation.
Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
levels have been shown to relate to aggression and sex drive. This helps create synaptogenesis by promoting neurite development and migration. Activin promotes neural plasticity throughout the lifespan and regulates the neurotransmitters of peripheral neurons. Environment can also affect hormones and behavior interaction. Women have more connections between areas of language better enabling them to communicate than men. On average men out perform women on spatial reasoning tests, which is theorized to result from sexual differences. Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. 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...
has been linked to aggression and sex drive; therefore men tend to be more competitive or aggressive than women. There is also a large amount of individual diversity within all these traits and hormone levels.
Gene mutations
Genetic mutations and chromosomal abnormalities are two sources of HPG axis alteration. Single mutations usually lead to changes in binding ability of the hormone and receptor leading to inactivation or over activation. These mutations can occur in the genes coding for GnRH, LH, and FSH or their receptors. Depending on which hormone and receptor are unable to bind different effects occur but all alter the HPG axis.For example, in males mutations in the GnRH coding gene could result in hypogonadotrophic hypogonadism. A mutation that cause a gain of function for LH receptor can result in a condition known as testotoxicosis, which cause puberty to occur between ages 2–3 years. Loss of function of LH receptors can cause male pseudohermaphroditism. In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.
Medications
Medications for diseases, conditions, and personal reasons often take advantage of the HPG axis. By altering hormones levels of the HPG axis, desirable effects can occur often along with side effects. Hormone levels can be altered in the case of hormonal birth control and hormone replacement therapyHormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
. Hormonally based birth control alters the HPG axis by mimicking the pregnancy state. The primary active ingredients are synthetic progesterones, which mimic biologically derived progesterone. The synthetic progesterone prevent the hypothalamus from releasing GnRH and the pituitary from releasing LH and FSH; therefore it prevents the ovarian cycle from entering the menstrual phase and prevents follicle development and ovulation. Also as a result, many of the side effects are similar to the symptoms of pregnancy. Hormone replacement therapy disrupt the HPG axis decline but focus more on estrogen. Alzheimer's has been shown to have a hormonal component, which could possibly be used to a method of prevent the disease.