Anatomic distribution of kisspeptin neurons in the adult sheep amygdala: Associations with sex, estrogen receptor alpha, androgen receptor, and sexual partner preference

Abstract

Kisspeptin neurons are primarily known for regulating reproductive function by stimulating hormone release that controls puberty and fertility. While typically associated with the hypothalamus, recent research suggests their presence in other brain regions, including the amygdala. The amygdala, crucial for emotional processing and social behaviors, consists of various nuclei. However, the specific distribution and potential functional implications of kisspeptin neurons within this region remain unclear. Understanding kisspeptin neuron distribution in the sheep amygdala could provide insights into their roles in modulating reproductive functions, emotional, and social behaviors in a species closely related to humans. This study employed immunohistochemistry and RNAscope™ fluorescent in situ hybridization to map the distribution of kisspeptin fibers and cells in the amygdala of intact adult male and luteal-phase female sheep. The research also investigated the co-expression of Kiss1 with estrogen receptor-α (ESR1) and androgen receptor (AR) mRNA, as well as the presence of kisspeptin receptor (Kiss1r) mRNA-containing cells. Kisspeptin immunoreactive fibers were most dense in the medial amygdala, while Kiss1 mRNA-containing cells were abundant in the medial, cortical, and basal nuclei. Extensive co-expression of Kiss1 with ESR1 and AR mRNA was observed. In the posterior medial nucleus, 80% of kisspeptin neurons co-expressed ESR1, and 40% co-expressed AR. Kiss1r mRNA-containing cells were found in the medial, cortical, and basal nuclei and co-localized within cells expressing Kiss1 mRNA. No differences in kisspeptin cell numbers were found between rams and ewes or between rams with different sexual partner preferences. This study provides a foundational map of the kisspeptin system in the sheep amygdala, offering insights into its potential roles in reproductive, emotional, and social behaviors. The extensive co-expression of Kiss1 mRNA with ESR1 and AR mRNA suggests possible regulation by sex steroids, while the presence of Kiss1r mRNA-containing cells indicates potential autocrine or paracrine signaling. These findings contribute to our understanding of kisspeptin neurons' distribution and potential functions beyond the hypothalamus, particularly in the amygdala.