KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season

Endocrinology. 2007 Mar;148(3):1150-7. doi: 10.1210/en.2006-1435. Epub 2006 Dec 21.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Estradiol / pharmacology
  • Female
  • Gene Expression Regulation* / drug effects
  • Gonadal Steroid Hormones / physiology*
  • Hypothalamus / metabolism*
  • Ovariectomy
  • Progesterone / pharmacology
  • RNA, Messenger / metabolism
  • Seasons*
  • Sheep / metabolism*
  • Tissue Distribution
  • Tumor Suppressor Proteins / metabolism*


  • Gonadal Steroid Hormones
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Progesterone
  • Estradiol