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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.
The arcuate nucleus of the hypothalamus (ARH), or ARC, is also known as the infundibular nucleus to distinguish it from the arcuate nucleus of the medulla oblongata in the brainstem. The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.
Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.
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 principal 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.
A gonadotropin-releasing hormone 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 treatment of hormone-sensitive cancers such as prostate cancer and breast cancer, certain gynecological disorders like heavy periods and endometriosis, high testosterone levels in women, early puberty in children, as a part of transgender hormone therapy, and to delay puberty in transgender youth among other uses. It is also used in the suppression of spontaneous ovulation as part of controlled ovarian hyperstimulation, an essential component in IVF. GnRH agonists are given by injections into fat, as implants placed into fat, and as nasal sprays.
Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors.
Signaling peptide receptor is a type of receptor which binds one or more signaling peptides or signaling proteins.
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.
Urotensin-II (U-II) is a peptide ligand that is the strongest known vasoconstrictor. Because of the involvement of the UII system in multiple biological systems such as the cardiovascular, nervous, endocrine, and renal, it represents a promising target for the development of new drugs.
The KiSS1-derived peptide receptor is a G protein-coupled receptor which binds the peptide hormone kisspeptin (metastin). Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues. Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.
The neuropeptide FF receptors are members of the G-protein coupled receptor superfamily of integral membrane proteins which bind the pain modulatory neuropeptides AF and FF. The Neuropeptide FF receptor family is a member of the G protein-coupled receptor superfamily containing two subtypes, NPFF1 and NPFF2, which exhibit a high affinity for Neuropeptide FF (NPFF) peptides. NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density, particularly in mammals in the superficial layers of the spinal cord where it is involved in nociception and modulation of opioid functions. These receptors participate to the modulation of opioid receptor function in the brain and spinal cord, and can either reduce or increase opioid receptor function depending which tissue they are released in, reflecting a complex role for neuropeptide FF in pain responses.
Neuropeptide FF receptor 2, also known as NPFF2 is a human protein encoded by the NPFFR2 gene.
Neuropeptide FF is a mammalian amidated neuropeptide originally isolated from bovine brain and characterized as a pain-modulating peptide, with anti-opioid activity on morphine-induced analgesia.
RF(Arg-Phe)amide family 26 amino acid peptide, also known as P518, is a human protein.
The hormone of gonadotropins secreted by the anterior hypophyse gland effects on the gonads and play a crucial role in the process of gonadal development and function in vertebrates. In birds and mammals, luteinizinghormone (LH) regulates sex steroid production as well as ovulation, whereas follicle stimulating hormone (FSH) promotes spermatogenesis and ovarian follicle maturation. Since the isolation of gonadotropin-releasing hormone (GnRH), a hypothalamic decapeptide, from mammalian brain in the early 1970s, several other GnRHs have been identified in the brains of other vertebrates. Based on extensive studies in vertebrates, it was generally believed that GnRH is the only hypothalamic regulator of the release of pituitary gonadotropins. Some neurochemicals and peripheral hormones [e.g.gamma-aminobutyric acid (GABA), opiates, gonadal sex steroids, inhibin] can modulate gonadotropin release, but GnRH was considered to have no hypothalamic antagonist.
Sufugolix (INNTooltip International Nonproprietary Name, BANTooltip British Approved Name) (developmental code name TAK-013) is a non-peptide, orally-active, selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (IC50Tooltip Half-maximal inhibitory concentration = 0.1 and 0.06 nM for affinity and in vitro inhibition, respectively). It was under development by Takeda for the treatment of endometriosis and uterine leiomyoma and reached phase II clinical trials for both of these indications, but was subsequently discontinued. It seems to have been supplanted by relugolix (TAK-385), which is also under development by Takeda for the treatment of these conditions and has a more favorable drug profile (including reduced cytochrome P450 inhibition and improved in vivo GnRHR antagonistic activity) in comparison.
The RFamide peptide family, or the RFamide-related peptides (RFRPs), are a family of neuropeptides. They are characterized by the possession of an Arg-Phe-NH2 motif at their C-terminal extremities.
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.
Gonadotropin-inhibitory hormone (GnIH) is a RFamide-related peptide coded by the NPVF gene in mammals.
References
- 1 2 Jae Young Seong; Hubert Vaudry (7 November 2014). Neuropeptide GPCRs in neuroendocrinology. Frontiers E-books. pp. 226–. ISBN 978-2-88919-267-0.
- 1 2 3 Hinuma S, Shintani Y, Fukusumi S, Iijima N, Matsumoto Y, Hosoya M, Fujii R, Watanabe T, Kikuchi K, Terao Y, Yano T, Yamamoto T, Kawamata Y, Habata Y, Asada M, Kitada C, Kurokawa T, Onda H, Nishimura O, Tanaka M, Ibata Y, Fujino M (2000). "New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals". Nat. Cell Biol. 2 (10): 703–8. doi:10.1038/35036326. PMID 11025660. S2CID 2580390.
- ↑ Gouardères C, Mazarguil H, Mollereau C, Chartrel N, Leprince J, Vaudry H, Zajac JM (2007). "Functional differences between NPFF1 and NPFF2 receptor coupling: high intrinsic activities of RFamide-related peptides on stimulation of [35S]GTPgammaS binding". Neuropharmacology. 52 (2): 376–86. doi:10.1016/j.neuropharm.2006.07.034. PMID 17011599. S2CID 140207990.
- ↑ Murakami M, Matsuzaki T, Iwasa T, Yasui T, Irahara M, Osugi T, Tsutsui K (2008). "Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats". J. Endocrinol. 199 (1): 105–12. doi: 10.1677/JOE-08-0197 . PMID 18653621.
- ↑ Clarke IJ, Qi Y, Puspita Sari I, Smith JT (2009). "Evidence that RF-amide related peptides are inhibitors of reproduction in mammals". Front Neuroendocrinol. 30 (3): 371–8. doi:10.1016/j.yfrne.2009.04.001. PMID 19362107. S2CID 7890470.
- ↑ Pineda R, Garcia-Galiano D, Sanchez-Garrido MA, Romero M, Ruiz-Pino F, Aguilar E, Dijcks FA, Blomenröhr M, Pinilla L, van Noort PI, Tena-Sempere M (2010). "Characterization of the potent gonadotropin-releasing activity of RF9, a selective antagonist of RF-amide-related peptides and neuropeptide FF receptors: physiological and pharmacological implications". Endocrinology. 151 (4): 1902–13. doi: 10.1210/en.2009-1259 . PMID 20160130.
