title: KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season.
abstract: The KiSS-1 gene encodes a family of peptides called kisspeptins, which are endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function appears to be critical for GnRH secretion and the initiation of puberty. To test the hypothesis that steroid hormones regulate KiSS-1 mRNA expression in the ewe, we examined the brains of ovary-intact (luteal phase) and ovariectomized (OVX) ewes, as well as OVX ewes that received estradiol (E) or progesterone (P) replacement. KiSS-1 mRNA-expressing cells were predominantly located in the arcuate nucleus (ARC). Here, expression was increased after OVX but returned to the level of gonad-intact animals with E treatment. Treatment with P partially restored KiSS-1 expression toward gonad-intact levels. Double-label immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive cells in the ARC are also P-receptor positive. Finally, we tested the hypothesis that KiSS-1 mRNA is lower during anestrus, due to a non-steroid-dependent seasonal effect. In OVX ewes, expression in the ARC was lower at the time of year corresponding to anestrus. We conclude that KiSS-1 expression in the ARC of the ewe brain is negatively regulated by chronic levels of E and P, suggesting that both steroids may exert negative feedback control on GnRH secretion through altered kisspeptin signaling. Furthermore, a seasonal alteration in KiSS-1 expression in the ARC of OVX ewes strongly suggests that kisspeptin is fundamentally involved in the control of seasonal changes in reproductive function.
authors.affiliation: Department of Physiology, P.O. Box 13F, Monash University, Victoria 3800, Australia. iain.clarke@med.monash.edu.au.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Smith
authors.forename: Colin M
authors.initials: CM
authors.lastname: Clay
authors.forename: Alain
authors.initials: A
authors.lastname: Caraty
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Clarke
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012621:Seasons; D012756:Sheep / Q000378:metabolism*; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D011374:Progesterone; D004958:Estradiol