Decrease in Hypothalamic Kiss1 and Kiss1r Expression: A Potential Mechanism for Fasting-induced Suppression of the HPG Axis in the Adult Male Rhesus Monkey (Macaca mulatta)

Fasting suppresses functioning of the hypothalamic-pituitary-gonadal (HPG) axis by mechanisms that are incompletely understood. In 2003, hypothalamic kisspeptin-Kiss1r signaling was discovered to play a significant role in regulating the HPG axis. We have recently shown that in adult male macaques, short-term fasting attenuates the response of the HPG axis to an exogenous kisspeptin challenge. In the present study, we explored the mechanism underlying this attenuated response by examining the modulation of the hypothalamic expression of Kiss1 and Kiss1r under short-term fasting and normal feeding conditions in the adult male macaques. Hypothalamic mRNA was extracted from normal fed (n=3) and 48-h fasted (n=3) monkeys. Kiss1, Kiss1r, and GnRH1 mRNA was quantified by reverse transcription followed by real-time polymerase chain reaction. In addition, blood samples were collected for measurement of plasma concentrations of glucose, cortisol, leptin, and testosterone. In contrast to fed animals, plasma glucose, leptin, and testosterone levels decreased and cortisol levels increased in fasted animals. The hypothalamic expression of Kiss1 and Kiss1r mRNA was significantly lower (P<0.05) in fasted monkeys compared to fed monkeys while hypothalamic GnRH1 mRNA expression was comparable between the two groups. Thus, our results demonstrate that expression of hypothalamic Kiss1 and Kiss1r decrease after a short-term fasting in monkeys. This decrease may contribute to the suppression of the HPG axis during fasting conditions in primates. In addition, our finding of lower expression of Kiss1r in fasted monkeys provides an explanation for the attenuation in the HPG axis response to peripheral kisspeptin challenge during short-term fasting.