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Submitted on October 26, 2006
Accepted on December 11, 2006
Department of Physiology, Monash University, Victoria, 3880, Australia; Department of Biomedical Sciences, Colorado State University, Fort Collins 80523, USA; UMR 6175 INRA/CNRS/UniversityTours/Haras Nationaux, IFR 135, Nouzilly, France
* To whom correspondence should be addressed. E-mail: iain.clarke{at}med.monash.edu.au.
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 gonadotropin-releasing hormone 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 ovariectomy, but returned to the level of gonad-intact animals with E treatment. Treatment with P partially restored KiSS-1 expression towards gonad-intact levels. Double-label immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive cells in the ARC are also progesterone receptor (PR)-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 signalling. 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.
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