Gonadotropin-releasing hormone

Gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)

from PDB 1YY1
Identifiers
Symbols GNRH1; GNRH; GRH; LHRH; LNRH
External IDs OMIM152760 MGI95789 HomoloGene641 GeneCards: GNRH1 Gene
RNA expression pattern
PBB GE GNRH1 207987 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2796 14714
Ensembl ENSG00000147437 ENSMUSG00000015812
UniProt P01148 Q14AC4
RefSeq (mRNA) NM_000825.3 NM_008145.2
RefSeq (protein) NP_000816.3 NP_032171.1
Location (UCSC) Chr 8:
25.28 – 25.28 Mb
Chr 14:
68.36 – 68.37 Mb
PubMed search [1] [2]

Gonadotropin-releasing hormone (GnRH), also known as Luteinizing-hormone-releasing hormone (LHRH) and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is synthesized and released from neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family.

Contents

Production

The gene, GNRH1, for the GnRH precursor is located on chromosome 8. In mammals, the linear decapeptide end-product is synthesized from a 92-amino acid preprohormone in the preoptic anterior hypothalamus.

Structure

The identity of GnRH was clarified by the 1977 Nobel Laureates Roger Guillemin and Andrew V. Schally:

pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2

GnRH as a neurohormone

GnRH is considered a neurohormone, a hormone produced in a specific neural cell and released at its neural terminal. A key area for production of GNRH is the preoptic area of the hypothalamus, which contains most of the GnRH-secreting neurons. GnRH neurons originate in the nose and migrate into the brain, where they are scattered throughout the medial septum and hypothalamus and connected by very long >1-millimeter-long dendrites. These bundle together so they receive shared synaptic input, a process that allows them to synchronize their GnRH release.[1]

GnRH is secreted in the hypophysial portal bloodstream at the median eminence. The portal blood carries the GnRH to the pituitary gland, which contains the gonadotrope cells, where GnRH activates its own receptor, gonadotropin-releasing hormone receptor (GnRHR), a seven-transmembrane G-protein-coupled receptor that stimulates the beta isoform of Phosphoinositide phospholipase C, which goes on to mobilize calcium and protein kinase C. This results in the activation of proteins involved in the synthesis and secretion of the gonadotropins LH and FSH. GnRH is degraded by proteolysis within a few minutes.

Control of FSH and LH

At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate LH release.

There are differences in GnRH secretion between females and males. In males, GnRH is secreted in pulses at a constant frequency, but, in females, the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation.

GnRH secretion is pulsatile in all vertebrates, and is necessary for correct reproductive function. Thus, a single hormone, GnRH1, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male.

Activity

GnRH activity is very low during childhood, and is activated at puberty. During the reproductive years, pulse activity is critical for successful reproductive function as controlled by feedback loops. However, once a pregnancy is established, GnRH activity is not required. Pulsatile activity can be disrupted by hypothalamic-pituitary disease, either dysfunction (i.e., hypothalamic suppression) or organic lesions (trauma, tumor). Elevated prolactin levels decrease GnRH activity. In contrast, hyperinsulinemia increases pulse activity leading to disorderly LH and FSH activity, as seen in polycystic ovary syndrome (PCOS). GnRH formation is congenitally absent in Kallmann syndrome.

The GnRH neurons are regulated by many different afferent neurons, using several different transmitters (including norepinephrine, GABA, glutamate). For instance, dopamine appears to stimulate LH release (through GnRH) in estrogen-progesterone-primed females; dopamine may inhibit LH release in ovariectomized females.[2] Kisspeptin appears to be an important regulator of GnRH release.[3] GnRH release can also be regulated by estrogen. It has been reported that there are kisspeptin-producing neurons that also express estrogen receptor alpha.[4]

GnRH in other organs

GnRH is found in organs outside of the hypothalamus and pituitary, and its role in other life processes is poorly understood. For instance, there is likely to be a role for GnRH1 in the placenta and in the gonads. GnRH and GnRH receptors are also found in cancers of the breast, ovary, prostate, and endometrium.[5]

Medication

GnRH is available as gonadorelin hydrochloride(Factrel®)and gonadorelin diacetate tetrahydrate(Cystorelin®)for injectable use. Studies have described it being used via an infusion pump system to induce ovulation in patients with hypothalamic hypogonadism. It is also used in veterinary medicine as a treatment for cattle with cystic ovarian disease.

Its analogue Leuprolide is used for continuous infusion, to treat Breast carcinoma, endometriosis, prostate carcinoma, and precocious puberty.

Agonists and antagonists

While GnRH has been synthesized and become available, its short half-life requires infusion pumps for its clinical use. Modifications of the decapeptide structure of GnRH have led to GnRH1 analog medications that either stimulate (GnRH1 agonists) or suppress (GnRH antagonists) the gonadotropins. It is important to note that, through downregulation, agonists are also able to exert a prolonged suppression effect.

References

  1. ^ Campbell RE, Gaidamaka G, Han SK, Herbison AE (June 2009). "Dendro-dendritic bundling and shared synapses between gonadotropin-releasing hormone neurons". Proc. Natl. Acad. Sci. U.S.A. 106 (26): 10835–40. doi:10.1073/pnas.0903463106. PMC 2705602. PMID 19541658. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2705602. 
  2. ^ Brown RM (1994). An introduction to Neuroendocrinology. Cambridge, UK: Cambridge University Press. ISBN 0-521-42665-0. 
  3. ^ Dungan HM, Clifton DK, Steiner RA (March 2006). "Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion". Endocrinology 147 (3): 1154–8. doi:10.1210/en.2005-1282. PMID 16373418. 
  4. ^ Franceschini I, Lomet D, Cateau M, Delsol G, Tillet Y, Caraty A (July 2006). "Kisspeptin immunoreactive cells of the ovine preoptic area and arcuate nucleus co-express estrogen receptor alpha". Neurosci. Lett. 401 (3): 225–30. doi:10.1016/j.neulet.2006.03.039. PMID 16621281. 
  5. ^ Schally AV (1999). "Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis.". Peptides 20 (10): 1247–62. doi:10.1016/S0196-9781(99)00130-8. PMID 10573298. 

Further reading



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Look at other dictionaries:

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  • gonadotropin releasing hormone — 1. Biochem. a peptide hormone, produced by the hypothalamus, that stimulates the anterior lobe of the pituitary gland to secrete luteinizing hormone and follicle stimulating hormone. 2. Pharm. a preparation of this hormone, used to treat… …   Universalium

  • gonadotropin releasing hormone — 1. Biochem. a peptide hormone, produced by the hypothalamus, that stimulates the anterior lobe of the pituitary gland to secrete luteinizing hormone and follicle stimulating hormone. 2. Pharm. a preparation of this hormone, used to treat… …   Useful english dictionary

  • gonadotropin-releasing hormone — gonadotropin re·leas·ing hormone ri lēs iŋ n a decapeptide hormone produced by the hypothalamus that stimulates the adenohypophysis to release gonadotropins (as luteinizing hormone and follicle stimulating hormone) abbr. GnRH called also… …   Medical dictionary

  • gonadotropin-releasing hormone — ˌ ̷ ̷ (ˌ) ̷ ̷  ̷ ̷ ˈ ̷ ̷  ̷ ̷  ̷ ̷ ˈ ̷ ̷  ̷ ̷ noun : a decapeptide hormone produced by the hypothalamus that stimulates the adenohypophysis to release gonadotropins (as luteinizing hormone and follicle stimulating hormone) called also luteinizing …   Useful english dictionary

  • gonadotropin-releasing hormone — noun Date: 1974 a hormone secreted by the hypothalamus that stimulates the anterior lobe of the pituitary gland to release gonadotropins (as luteinizing hormone and follicle stimulating hormone) abbreviation GnRH; called also luteinizing hormone… …   New Collegiate Dictionary

  • gonadotropin-releasing hormone — GnRH. A hormone made by the hypothalamus (part of the brain). GnRH causes the pituitary gland to make luteinizing hormone (LH) and follicle stimulating hormone (FSH). These hormones are involved in reproduction. Also called GnRH …   English dictionary of cancer terms

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