Variation in kisspeptin and RFamide-Related Peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: A novel medium for seasonal breeding in the sheep

Jeremy Troy Smith, Lique M Coolen, Lance J Kriegsfeld, Ika Puspita Sari, Mohammad R Jafarzadehshirazi, Matthew Maltby, Katherine Bateman, Robert L Goodman, Alan John Tilbrook, Takayoshi Ubuka, George Edward Bentley, Iain James Clarke, Michael N Lehman

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304 Citations (Scopus)


Reproductive activity in sheep is seasonal, being activated by short-day photoperiods and inhibited by long days. During the non-breeding season, gonadotropin-releasing hormone (GnRH) secretion is reduced by both steroid-independent and steroid-dependent (increased response to estradiol negative feedback) effects of photoperiod. Kisspeptin (also known as metastin) and gonadotropin-inhibitory hormone (GnIH, or RFRP) are two RFamide neuropeptides that appear critical in the regulation of the reproductive neuroendocrine axis. We hypothesized that expression of kisspeptin and/or GnIH underlies the seasonal change in GnRH secretion. We examined kisspeptin and GnIH (protein and mRNA) expression in the brains of ovariectomized (OVX) ewes treated with estradiol (OVX+E) during the non-breeding and breeding seasons. In OVX+E ewes, greater expression of kisspeptin and Kiss1 mRNA in the arcuate nucleus and lesser expression of GnIH (protein) in the dorsomedial nucleus of the hypothalamus were concurrent with the breeding season. There was also a greater number of kisspeptin terminal contacts onto GnRH neurons and less GnIH-GnRH contacts during the breeding season (compared to the non-breeding season) in OVX+E ewes. Comparison of OVX and OVX+E ewes in the breeding and non-breeding season revealed a greater effect of steroid replacement on inhibition of kisspeptin protein and Kiss1 mRNA expression during the non-breeding season. Overall, we propose that the two RFamide peptides, kisspeptin and GnIH, act in concert, with opposing effects, to regulate the activity of GnRH neurons across the seasons, leading to the annual change in fertility and the cyclical seasonal transition from non-breeding to breeding season.
Original languageEnglish
Pages (from-to)5770 - 5782
Number of pages13
Issue number11
Publication statusPublished - 2008

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