KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season

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 expre...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2007-03, Vol.148 (3), p.1150-1157
Main Authors: Smith, Jeremy T, Clay, Colin M, Caraty, Alain, Clarke, Iain J
Format: Article
Language:English
Subjects:
Animals
Arcuate Nucleus of Hypothalamus - drug effects
Arcuate Nucleus of Hypothalamus - metabolism
Biological and medical sciences
Endocrinology and metabolism
Estradiol - pharmacology
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Gonadal Steroid Hormones - physiology
Human health and pathology
Hypothalamus - metabolism
Life Sciences
Ovariectomy
Progesterone - pharmacology
RNA, Messenger - metabolism
Seasons
Sheep - metabolism
Tissue Distribution
Tumor Suppressor Proteins - metabolism
Vertebrates: endocrinology
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Summary: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.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2006-1435