Gonadotrophin
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Gonadotropins are
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s secreted by
gonadotropic cell Gonadotropic cells (called also Gonadotropes or Gonadotrophs or Delta Cells or Delta basophils) are endocrine cells in the anterior pituitary that produce the gonadotropins, such as the follicle-stimulating hormone (FSH) and luteinizing hormone (L ...
s of the
anterior pituitary A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
of
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s. This family includes the
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
ian hormones
follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) and
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH), the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
l/
chorion The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It develops from an outer fold on the surface of the yolk sac, which lies outside the zona pellucida (in mammals), known as the vitelline ...
ic gonadotropins,
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(hCG) and
equine chorionic gonadotropin Equine chorionic gonadotropin (acronym given as eCG but not to be confused with ECG) is a gonadotropin, gonadotropic hormone produced in the chorion of pregnant mares. Previously referred to as pregnant mare's Blood serum, serum gonadotropin (PMSG), ...
(eCG), as well as at least two forms of
fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of li ...
gonadotropins. These hormones are central to the complex
endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
that regulates normal
growth Growth may refer to: Biology * Auxology, the study of all aspects of human physical growth * Bacterial growth * Cell growth * Growth hormone, a peptide hormone that stimulates growth * Human development (biology) * Plant growth * Secondary growth ...
,
sexual development Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. In ...
, and reproductive function. LH and FSH are secreted by the anterior
pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
, while hCG and eCG are secreted by the placenta in
pregnant Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
humans and
mare A mare is an adult female horse or other equine. In most cases, a mare is a female horse over the age of three, and a filly is a female horse three and younger. In Thoroughbred horse racing, a mare is defined as a female horse more than four ...
s, respectively. The gonadotropins act on the
gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...
s, controlling
gamete A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce t ...
and
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects ar ...
production. Gonadotropin is sometimes abbreviated ''Gn''. The alternative spelling ''gonadotrophin'' which inaccurately implies a nourishing mechanism is also used. There are various preparations of gonadotropins for
therapeutic A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...
use, mainly as
fertility medication Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
. There are also
fad diet A fad diet is a diet that becomes popular for a short time, similar to fads in fashion, without being a standard dietary recommendation, and often making unreasonable claims for fast weight loss or health improvements. There is no single defini ...
or
quack Quack, The Quack or Quacks may refer to: People * Quack Davis, American baseball player * Hendrick Peter Godfried Quack (1834–1917), Dutch economist and historian * Joachim Friedrich Quack (born 1966), German Egyptologist * Johannes Quack (b ...
preparations, which are illegal in various countries.


Natural types and subunit structure

The two principal gonadotropins in vertebrates are
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH) and
follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH), although primates produce a third gonadotropin called
chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(CG). LH and FSH are heterodimers consisting of two
peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...
chains, an alpha chain and a beta chain. LH and FSH share nearly identical alpha chains (about 100 amino acids long), whereas the beta chain provides specificity for
receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
interactions. These subunits are heavily modified by
glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...
. The alpha subunit is common to each protein dimer (well conserved within species, but differing between them), and a unique beta subunit confers biological specificity. The alpha chains are highly conserved proteins of about 100 amino acid residues which contain ten conserved cysteines all involved in disulfide bonds, as shown in the following schematic representation. +---------------------------+ +----------+, +-------------, --+ , , , , , , , , , , +------, -----------------+ , , , +----------------------------+ 'C': conserved cysteine involved in a disulphide bond. Intracellular levels of free alpha subunits are greater than those of the mature glycoprotein, implying that hormone assembly is limited by the appearance of the specific beta subunits, and hence that synthesis of alpha and beta is independently regulated. Another human gonadotropin is
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
(hCG), produced by the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
.


Mechanism

Gonadotropin receptor The gonadotropin receptors are a group of receptors that bind a group of pituitary hormones called gonadotropins. They include the: * Follicle-stimulating hormone receptor (FSHR) - binds follicle-stimulating hormone (FSH) * Luteinizing hormone ...
s are embedded in the surface of the target
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s and coupled to the
G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
system. Signals triggered by binding to the receptor are relayed within the cells by the
cyclic AMP Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...
second messenger system. Gonadotropins are released under the control of
gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...
(GnRH) from the arcuate nucleus and preoptic area of the
hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
. The
gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...
s —
testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
and
ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
— are the primary target organs for LH and FSH. The gonadotropins affect multiple cell types and elicit multiple responses from the target organs. As a simplified generalization, LH stimulates the
Leydig Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
cells of the testes and the
theca cell The theca folliculi comprise a layer of the ovarian follicles. They appear as the follicles become secondary follicles. The theca are divided into two layers, the theca interna and the theca externa. Theca cells are a group of endocrine cells ...
s of the ovaries to produce
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
(and indirectly
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
), whereas FSH stimulates the spermatogenic tissue of the
testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
and the
granulosa cell A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals. Structure and function In the primordial ovarian follicle, an ...
s of
ovarian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with th ...
s, as well as stimulating production of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
by the ovaries. Although gonadotropins are secreted in a
pulsatile In fluid dynamics, a flow with periodic variations is known as pulsatile flow, or as Womersley flow. The flow profiles was first derived by John R. Womersley (1907–1958) in his work with blood flow in arteries. The cardiovascular system of chord ...
manner (as a result of pulsatile GnRH release), unlike the case of GnRH and
GnRH agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
s, constant/non-pulsatile activation of the gonadotropin receptors by the gonadotropins does not produce functional inhibition. This can be seen during the first 7–10 weeks of pregnancy, where constantly high and progressively-increasing levels of hCG circulate and mediate production of estrogen and progesterone by the
corpus luteum The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
until the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
takes over the production of these hormones.


Diseases

Gonadotropin deficiency due to
pituitary In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypop ...
disease results in
hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...
, which can lead to
infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
. Treatment includes administered gonadotropins, which, therefore, work as
fertility medication Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
. Such can either be produced by extraction and purification from urine or be produced by
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be foun ...
. Failure or loss of the gonads usually results in elevated levels of LH and FSH in the blood. LH insensitivity, which results in
Leydig cell hypoplasia Leydig cell hypoplasia (or aplasia) (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 genetic males. It is characterized by an inability of the body to ...
in males, and FSH insensitivity, are conditions of insensitivity to LH and FSH, respectively, caused by
loss-of-function mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
s in their respective signaling receptors. Another closely related condition to these is GnRH insensitivity.


Pharmaceutical preparations

There are various preparations of gonadotropins for
therapeutic A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...
use, mainly as
fertility medication Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
. For example, the so-called
menotropin Menotropin (also called human menopausal gonadotropin or hMG) is a hormonally active medication for the treatment of fertility disturbances. Frequently the plural is used as the medication is a mixture of gonadotropins. Menotropins are extracted ...
s (also called ''human menopausal gonadotropins'') consist of LH and FSH extracted from the
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...
of
menopausal Menopause, also known as the climacteric, is the time in women's lives when Menstruation, menstrual periods stop permanently, and they are no longer fertility, able to bear children. Menopause usually occurs between the age of 47 and 54. Medic ...
women. There are also recombinant variants. Besides the aforementioned legitimate
pharmaceutical drug A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
s, there are
fad diet A fad diet is a diet that becomes popular for a short time, similar to fads in fashion, without being a standard dietary recommendation, and often making unreasonable claims for fast weight loss or health improvements. There is no single defini ...
or
quack Quack, The Quack or Quacks may refer to: People * Quack Davis, American baseball player * Hendrick Peter Godfried Quack (1834–1917), Dutch economist and historian * Joachim Friedrich Quack (born 1966), German Egyptologist * Johannes Quack (b ...
preparations, which are illegal in various countries.


See also

*
Antigonadotropin An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituita ...
* Gonadotropin surge-attenuating factor


References


External links

*
10th International Symposium on GnRH
{{Authority control Peptide hormones Hormones of the hypothalamus-pituitary-gonad axis Gonadotropin-releasing hormone and gonadotropins Animal reproductive system Sex hormones