GPR54 and kisspeptins.
The G-protein coupled receptor GPR54 has an essential role in the initiation and maintenance of mammalian fertility. Humans and mice with mutations in GPR54 have hypogonadotropic hypogonadism characterized by absence of sexual maturation and low levels of gonadotropic hormones (LH and FSH). The ligand for GPR54 is encoded by the KISS1 gene, which produces a 54-amino-acid peptide (metastin or kisspeptin-54) that can be cleaved into shorter peptides (kisspeptins 14, 13 and 10) with similar potencies. Kisspeptin administration stimulates gonadotropin release in several species by inducing GnRH secretion from hypothalamic GnRH neurons expressing GPR54. Kisspeptins are produced by neurons located in the AVPV and ARC regions of the hypothalamus. Expression of Kiss1 in these neurons is differentially regulated by sex steroids providing a mechanism by which testosterone or estrogen can regulate GnRH release. The AVPV region is sexually dimorphic with highest expression of kisspeptin in females. Positive feedback by estrogen on expression of Kiss1 in the AVPV region may be responsible for the pre-ovulatory LH surge during the estrus cycle. Central administration of kisspeptin to immature female rats can induce precocious activation of the gonadotropic axis, causing advanced vaginal opening, elevated uterus weight, increased serum levels of LH and estrogen and induce ovulation. Kisspeptins/GPR54 have also been implicated in regulating the estrus cycle of seasonal breeders and in the control of lactational amenorrhea. Expression of Gpr54 and Kiss1 have also been reported in several peripheral tissues including the pituitary, ovary, testes and the placenta raising the possibility that these genes may have additional functions in these tissues. Regulation of kisspeptin expression by peripheral factors such as leptin may be involved in coordinating metabolic status with the reproductive axis.
Colledge
W H
WH
Physiological Laboratory, Dept. of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Whc23@cam.ac.uk
D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism* / Q000502:physiology*; D000074502:Receptors, Kisspeptin-1; D012098:Reproduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins