Gonadotropin-releasing hormone
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Location (UCSC) | Chr 8: 25.42 – 25.42 Mb | Chr 14: 67.98 – 67.99 Mb | |||||||
PubMed search | [3] | [4] |
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Gonadotropin-releasing hormone (GnRH) is a
Structure
The identity
As is standard for
Synthesis
The gene, GNRH1, for the GnRH precursor is located on chromosome 8. In mammals, the linear decapeptide end-product is synthesized from an 89-amino acid preprohormone in the preoptic anterior hypothalamus. It is the target of various regulatory mechanisms of the hypothalamic–pituitary–gonadal axis, such as being inhibited by increased estrogen levels in the body.
Function
GnRH is secreted in the
GnRH activity is very low during
Control of FSH and LH
At the pituitary, GnRH stimulates the synthesis and secretion of
There are differences in GnRH secretion between females and males. In males, GnRH is secreted in pulses at a constant frequency; however, in females, the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation.[10]
GnRH secretion is pulsatile in all vertebrates,[11] 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.
Neurohormone
GnRH is considered a
The
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
Effects of behavior
GnRH production/release is one of the few confirmed examples in which behavior influences hormones, rather than the other way around.[
Multiple neuronal regions in the limbic system send signals to the hypothalamus to modulate the amount of GnRH production and the frequency of pulses. This provides a possible explanation for why psychic influences typically affect female sexual function.[17]
Medical uses
Natural GnRH was previously prescribed as
Its analogue leuprorelin is used for continuous infusion, to treat breast cancer, endometriosis, prostate cancer, and following research in the 1980s by researchers, including Dr. Florence Comite of Yale University, it was used to treat precocious puberty.[20][21]
A Cochrane Review is available which investigates whether GnRH analogues, given before or alongside chemotherapy, could prevent damage to women's ovaries caused by chemotherapy.[22] GnRH agonists appear to be effective in protecting the ovaries during chemotherapy, in terms of menstruation recovery or maintenance, premature ovarian failure and ovulation.
Animal sexual behavior
GnRH activity influences a variety of sexual behaviors. Increased levels of GnRH facilitate sexual displays and behavior in females. GnRH injections enhance copulation solicitation (a type of courtship display) in
An elevation of GnRH raises males’ testosterone capacity beyond a male's natural testosterone level. Injections of GnRH in male birds immediately after an aggressive territorial encounter results in higher testosterone levels than is observed naturally during an aggressive territorial encounter.[25]
A compromised GnRH system has adverse effects on
Veterinary use
The natural hormone is also used in veterinary medicine as a treatment for cattle with cystic ovarian disease. The synthetic analogue deslorelin is used in veterinary reproductive control through a sustained-release implant.
Other names
As with many hormones, GnRH has been called by various names in the medical literature over the decades since its existence was first inferred. They are as follows:
- Gonadotropin-releasing factor (GnRF, GRF); Gonadotropin-releasing hormone (GnRH, GRH)
- Follicle-stimulating hormone-releasing factor (FRF, FSH-RF); Follicle-stimulating hormone-releasing hormone (FRH, FSH-RH)
- Luteinizing hormone-releasing factor (LRF, LHRF); Luteinizing hormone-releasing hormone (LRH, LHRH)
- Follicle-stimulating hormone and luteinizing hormone–releasing factor (FSH/LH-RF); Follicle-stimulating hormone and luteinizing hormone-releasing hormone (FSH/LH-RH)
- Luteinizing hormone and follicle-stimulating hormone–releasing factor (LH/FSH-RF); Luteinizing hormone and follicle-stimulating hormone-releasing hormone (LH/FSH-RH)
- Gonadorelin (INN for pharmaceutical form)
- Gonadoliberin
See also
- Gonadotropin-releasing hormone receptor § Agonists
- GnRH modulator
- Progonadotropin
- Gonadotropin surge-attenuating factor
- GNRH2, a similar gene
- Gonadotropin-inhibitory hormone
- Breastfeeding and fertility
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000147437 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015812 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- .
- ^ "The Nobel Prize in Physiology or Medicine 1977". www.nobelprize.org. Nobel Media AB 2014. Retrieved 24 June 2016.
- ^ PMID 19541658.
- ^ ISBN 978-0-521-42665-7.
- PMID 9096885.
- . Retrieved 5 November 2014.
- PMID 19609045.
- PMID 16373418.
- S2CID 37619383.
- S2CID 37855824.
- S2CID 9918871.
- PMID 12151363.
- ^ Mills EGA, O'Byrne KT, Comninos AN. The Roles of the Amygdala Kisspeptin System. Semin Reprod Med. 2019 Mar;37(2):64-70. doi: 10.1055/s-0039-3400462. Epub 2019 Dec 17. PMID 31847026.
- ^ Drugs.com Factrel: Consumer Drug Information
- ^ Drugs.com Cystorelin: FDA Professional Drug Information
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- PMID 3760417.
- PMID 30827035.
- S2CID 31523984.
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Further reading
- Flanagan CA, Millar RP, Illing N (May 1997). "Advances in understanding gonadotrophin-releasing hormone receptor structure and ligand interactions". Reviews of Reproduction. 2 (2): 113–20. PMID 9414473.
- Leung PC, Cheng CK, Zhu XM (April 2003). "Multi-factorial role of GnRH-I and GnRH-II in the human ovary". Molecular and Cellular Endocrinology. 202 (1–2): 145–53. S2CID 24945436.
- Gründker C, Emons G (October 2003). "Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer". Reproductive Biology and Endocrinology. 1: 65. PMID 14594454.
- Limonta P, Moretti RM, Montagnani Marelli M, Motta M (December 2003). "The biology of gonadotropin hormone-releasing hormone: role in the control of tumor growth and progression in humans". Frontiers in Neuroendocrinology. 24 (4): 279–95. S2CID 33327806.
- Janáky T, Juhász A, Bajusz S, Csernus V, Srkalovic G, Bokser L, Milovanovic S, Redding TW, Rékási Z, Nagy A (February 1992). "Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups". Proceedings of the National Academy of Sciences of the United States of America. 89 (3): 972–6. PMID 1310542.
- Healey SC, Martin NG, Chenevix-Trench G (November 1991). "NcoI RFLP of the human LHRH gene on chromosome 8p". Nucleic Acids Research. 19 (21): 6059. PMID 1682898.
- Williamson P, Lang J, Boyd Y (November 1991). "The gonadotropin-releasing hormone (Gnrh) gene maps to mouse chromosome 14 and identifies a homologous region on human chromosome 8". Somatic Cell and Molecular Genetics. 17 (6): 609–15. S2CID 41687915.
- Hayflick JS, Adelman JP, Seeburg PH (August 1989). "The complete nucleotide sequence of the human gonadotropin-releasing hormone gene". Nucleic Acids Research. 17 (15): 6403–4. PMID 2671939.
- Nikolics K, Mason AJ, Szönyi E, Ramachandran J, Seeburg PH (1985). "A prolactin-inhibiting factor within the precursor for human gonadotropin-releasing hormone". Nature. 316 (6028): 511–7. S2CID 4276604.
- Adelman JP, Mason AJ, Hayflick JS, Seeburg PH (January 1986). "Isolation of the gene and hypothalamic cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat". Proceedings of the National Academy of Sciences of the United States of America. 83 (1): 179–83. PMID 2867548.
- Yang-Feng TL, Seeburg PH, Francke U (January 1986). "Human luteinizing hormone-releasing hormone gene (LHRH) is located on short arm of chromosome 8 (region 8p11.2----p21)". Somatic Cell and Molecular Genetics. 12 (1): 95–100. S2CID 2067940.
- Seeburg PH, Adelman JP (1984). "Characterization of cDNA for precursor of human luteinizing hormone releasing hormone". Nature. 311 (5987): 666–8. S2CID 4286007.
- Tan L, Rousseau P (December 1982). "The chemical identity of the immunoreactive LHRH-like peptide biosynthesized in the human placenta". Biochemical and Biophysical Research Communications. 109 (3): 1061–71. PMID 6760865.
- Dong KW, Yu KL, Roberts JL (December 1993). "Identification of a major up-stream transcription start site for the human progonadotropin-releasing hormone gene used in reproductive tissues and cell lines". Molecular Endocrinology. 7 (12): 1654–66. PMID 8145771.
- Kakar SS, Jennes L (November 1995). "Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor mRNAs in various non-reproductive human tissues". Cancer Letters. 98 (1): 57–62. PMID 8529206.
- Nagy A, Schally AV, Armatis P, Szepeshazi K, Halmos G, Kovacs M, Zarandi M, Groot K, Miyazaki M, Jungwirth A, Horvath J (July 1996). "Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent". Proceedings of the National Academy of Sciences of the United States of America. 93 (14): 7269–73. PMID 8692981.
- Chegini N, Rong H, Dou Q, Kipersztok S, Williams RS (September 1996). "Gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in human myometrium and leiomyomata and the direct action of GnRH analogs on myometrial smooth muscle cells and interaction with ovarian steroids in vitro". The Journal of Clinical Endocrinology and Metabolism. 81 (9): 3215–21. S2CID 45976322.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Dong KW, Yu KL, Chen ZG, Chen YD, Roberts JL (July 1997). "Characterization of multiple promoters directing tissue-specific expression of the human gonadotropin-releasing hormone gene". Endocrinology. 138 (7): 2754–62. PMID 9202214.
- Twan WH, Hwang JS, Lee YH, Jeng SR, Yueh WS, Tung YH, Wu HF, Dufour S, Chang CF (January 2006). "The presence and ancestral role of gonadotropin-releasing hormone in the reproduction of scleractinian coral, Euphyllia ancora". Endocrinology. 147 (1): 397–406. PMID 16195400.