Gonadotropin-releasing hormone family

Last updated
Gonadotropin-releasing hormone
Identifiers
SymbolGnRH
Pfam PF00446
InterPro IPR002012
PROSITE PDOC00432

The gonadotropin-releasing hormones (GnRH) (gonadoliberin) [1] are a family of peptides that play a pivotal role in reproduction. The main function of GnRH is to act on the pituitary to stimulate the synthesis and secretion of luteinizing and follicle-stimulating hormones, but GnRH also acts on the brain, retina, sympathetic nervous system, gonads, and placenta in certain species. There seems to be at least three forms of GnRH. The second form is expressed in midbrain and seems to be widespread. The third form has been found so far only in fish. GnRH is a C-terminal amidated decapeptide processed from a larger precursor protein. Four of the ten residues are perfectly conserved in all species where GnRH has been sequenced.

Contents

Subfamilies

Human proteins containing this domain

GNRH1, GNRH2

Related Research Articles

Corticotropin-releasing factor family, CRF family is a family of related neuropeptides in vertebrates. This family includes corticotropin-releasing hormone, urotensin-I, urocortin, and sauvagine. The family can be grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and sauvagine in one group and CRH forming the other group. Urocortin and sauvagine appear to represent orthologues of fish urotensin-I in mammals and amphibians, respectively. The peptides have a variety of physiological effects on stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction in various species, and are all released as prohormones.

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 from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/chorionic gonadotropins, human chorionic gonadotropin (hCG) and equine chorionic gonadotropin (eCG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. LH and FSH are secreted by the anterior pituitary gland, while hCG and eCG are secreted by the placenta in pregnant humans and mares, respectively. The gonadotropins act on the gonads, controlling gamete and sex hormone production.

Releasing hormones and inhibiting hormones are hormones whose main purpose is to control the release of other hormones, either by stimulating or inhibiting their release. They are also called liberins and statins (respectively), or releasing factors and inhibiting factors. The examples are hypothalamic-pituitary hormones that can be classified from several viewpoints: they are hypothalamic hormones, they are hypophysiotropic hormones, and they are tropic hormones.

Gonadotropin-releasing hormone antagonist

Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.

The gonadotropin-releasing hormone receptor (GnRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is the receptor of gonadotropin-releasing hormone (GnRH). The GnRHR is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate.

Kisspeptin

Kisspeptins are proteins encoded by the KISS1 gene in humans. Kisspeptins are ligands of the G-protein coupled receptor, GPR54. Kiss1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. Kisspeptin-GPR54 signaling has an important role in initiating secretion of gonadotropin-releasing hormone (GnRH) at puberty, the extent of which is an area of ongoing research. Gonadotropin-releasing hormone is released from the hypothalamus to act on the anterior pituitary triggering the release of luteinizing hormone (LH), and follicle stimulating hormone (FSH). These gonadotropic hormones lead to sexual maturation and gametogenesis. Disrupting GPR54 signaling can cause hypogonadotrophic hypogonadism in rodents and humans. The Kiss1 gene is located on chromosome 1. It is transcribed in the brain, adrenal gland, and pancreas.

Neurokinin B Chemical compound

Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone. Additionally, NKB is associated with pregnancy in females and maturation in young adults. Reproductive function is highly dependent on levels of both neurokinin B and also the G-protein coupled receptor ligand kisspeptin. The first NKB studies done attempted to resolve why high levels of the peptide may be implicated in pre-eclampsia during pregnancy. NKB, kisspeptin, and dynorphin together are found in the arcuate nucleus (ARC) known as the KNDy subpopulation. This subpopulation is targeted by many steroid hormones and works to form a network that feeds back to GnRH pulse generator.

Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.

GNRHR2

Putative gonadotropin-releasing hormone II receptor is a protein that in humans is encoded by the GNRHR2 gene.

Secretin family receptor proteins, also known as Family B or family 2 of G-protein coupled receptors are regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.

GNRH2

Progonadoliberin-2 is a protein that in humans is encoded by the GNRH2 gene.

The gastrin family of proteins is defined by the peptide hormones gastrin and cholecystokinin. Gastrin and cholecystokinin (CCK) are structurally and functionally related peptide hormones that serve as regulators of various digestive processes and feeding behaviors. Additional structurally related members of this family include the amphibian caerulein skin peptide, the cockroach leukosulphakinin I and II (LSK) peptides, Drosophila melanogaster putative CCK-homologs Drosulphakinins I and II, cionin, a chicken gastrin/cholecystokinin-like peptide and cionin, a neuropeptide from the protochordate Ciona intestinalis.

Gonadotropin-releasing hormone (GnRH) insensitivity also known as Isolated gonadotropin-releasing hormone (GnRH)deficiency (IGD) is a rare autosomal recessive genetic and endocrine syndrome which is characterized by inactivating mutations of the gonadotropin-releasing hormone receptor (GnRHR) and thus an insensitivity of the receptor to gonadotropin-releasing hormone (GnRH), resulting in a partial or complete loss of the ability of the gonads to synthesize the sex hormones. The condition manifests itself as isolated hypogonadotropic hypogonadism (IHH), presenting with symptoms such as delayed, reduced, or absent puberty, low or complete lack of libido, and infertility, and is the predominant cause of IHH when it does not present alongside anosmia.

Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis. Hypothalamic disorders result from a deficiency in the release of gonadotropic releasing hormone (GnRH), while pituitary gland disorders are due to a deficiency in the release of gonadotropins from the anterior pituitary. GnRH is the central regulator in reproductive function and sexual development via the HPG axis. GnRH is released by GnRH neurons, which are hypothalamic neuroendocrine cells, into the hypophyseal portal system acting on gonadotrophs in the anterior pituitary. The release of gonadotropins, LH and FSH, act on the gonads for the development and maintenance of proper adult reproductive physiology. LH acts on Leydig cells in the male testes and theca cells in the female. FSH acts on Sertoli cells in the male and follicular cells in the female. Combined this causes the secretion of gonadal sex steroids and the initiation of folliculogenesis and spermatogenesis. The production of sex steroids forms a negative feedback loop acting on both the anterior pituitary and hypothalamus causing a pulsatile secretion of GnRH. GnRH neurons lack sex steroid receptors and mediators such as kisspeptin stimulate GnRH neurons for pulsatile secretion of GnRH.

Gonadotropin-releasing hormone modulator

A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing hormone. They include GnRH agonists and GnRH antagonists. These medications may be GnRH analogues like leuprorelin and cetrorelix – peptides that are structurally related to GnRH – or small-molecules like elagolix and relugolix, which are structurally distinct from and unrelated to GnRH analogues.

Ozarelix

Ozarelix is a peptide gonadotropin-releasing hormone antagonist which is or was under development by AEterna Zentaris Inc. and Spectrum Pharmaceuticals as a long-acting injection formulation for the treatment of prostate cancer. It has also been investigated for the treatment of endometriosis, but no development has been reported. The drug was previously under investigation for the treatment of benign prostatic hyperplasia and Alzheimer's disease as well, but development for these indications was discontinued. As of June 2015, it was in phase II clinical trials for prostate cancer. It seems to no longer be under development.

Gonadotropin surge-attenuating factor (GnSAF) is a nonsteroidal ovarian hormone produced by the granulosa cells of small antral ovarian follicles in females. GnSAF is involved in regulating the secretion of luteinizing hormone (LH) from the anterior pituitary and the ovarian cycle. During the early to mid-follicular phase of the ovarian cycle, GnSAF acts on the anterior pituitary to attenuate LH release, limiting the secretion of LH to only basal levels. At the transition between follicular and luteal phase, GnSAF bioactivity declines sufficiently to permit LH secretion above basal levels, resulting in the mid-cycle LH surge that initiates ovulation. In normally ovulating women, the LH surge only occurs when the oocyte is mature and ready for extrusion. GnSAF bioactivity is responsible for the synchronised, biphasic nature of LH secretion.

Kisspeptin, neurokinin B, and dynorphin (KNDy) neurons are neurons in the hypothalamus of the brain that are central to the hormonal control of reproduction.

Gonadotropin-inhibitory hormone (GnIH) is a RFamide-related peptide coded by the NPVF gene in mammals.

References

  1. Sherwood N (1987). "The GnRH family of peptides". Trends Neurosci. 10 (3): 129–132. doi:10.1016/0166-2236(87)90058-0. S2CID   53188553.
This article incorporates text from the public domain Pfam and InterPro: IPR002012