Gonadotropin-releasing hormone

Source: Wikipedia, the free encyclopedia.
GNRH1
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_001083111
NM_000825

NM_008145

RefSeq (protein)

NP_000816
NP_001076580

NP_032171

Location (UCSC)Chr 8: 25.42 – 25.42 MbChr 14: 67.98 – 67.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gonadotropin-releasing hormone (GnRH) is a

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

Structure

The identity

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

As is standard for

carboxamide
.

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

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.

GnRH activity is very low during

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
.

Control of FSH and LH

At the pituitary, GnRH stimulates the synthesis and secretion of

estrogens. Low-frequency GnRH pulses are required for FSH release, whereas high-frequency GnRH pulses stimulate LH pulses in a one-to-one manner.[9]

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

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.[7]

The

glutamate). For instance, dopamine appears to stimulate LH release (through GnRH) in estrogen-progesterone-primed females; dopamine may inhibit LH release in ovariectomized females.[8] Kisspeptin appears to be an important regulator of GnRH release.[12] GnRH release can also be regulated by estrogen. It has been reported that there are kisspeptin-producing neurons that also express estrogen receptor alpha.[13]

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

gonads. GnRH and GnRH receptors are also found in cancers of the breast, ovary, prostate, and endometrium.[14]

Effects of behavior

GnRH production/release is one of the few confirmed examples in which behavior influences hormones, rather than the other way around.[

GnRH neurons than either spawning or control females.[16] These examples suggest that GnRH is a socially regulated hormone.[citation needed
]

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

GnRH antagonists
) the gonadotropins. These synthetic analogs have replaced the natural hormone in clinical use.

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

Suncus murinus) reduced latency in displaying rump presents and tail wagging towards males.[24]

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

GnRH neurons are poor caregivers to their offspring. These mice are more likely to leave their pups scattered rather than grouped together, and will take significantly longer to retrieve their pups.[26]

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000147437 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015812 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. .
  6. ^ "The Nobel Prize in Physiology or Medicine 1977". www.nobelprize.org. Nobel Media AB 2014. Retrieved 24 June 2016.
  7. ^
    PMID 19541658
    .
  8. ^ .
  9. .
  10. . Retrieved 5 November 2014.
  11. .
  12. .
  13. .
  14. .
  15. .
  16. .
  17. ^ 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.
  18. ^ Drugs.com Factrel: Consumer Drug Information
  19. ^ Drugs.com Cystorelin: FDA Professional Drug Information
  20. PMID 6458765
    .
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  22. .
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  24. .
  25. .
  26. .

Further reading

External links