Arcuate Kisspeptin Neurons Play a Key Role in the Feedback Control of GnRH Secretion in Sheep.Robert L. Goodman, Ph.D.

Abstract

In rodents, two populations of kisspeptin neurons, one in the arcuate nucleus (ARC) and the other in the preoptic area (POA) appear to contribute to the feedback control of GnRH. In large mammals including sheep and primates, the majority of kisspeptin neurons are found in the ARC. In sheep, these kisspeptin neurons have several important characteristics. Anatomically, the ARC kisspeptin neurons also contain dynorphin and neurokinin-B, whereas POA kisspeptin neurons do not. Functionally, ARC kisspeptin neurons appear to play important roles in both the anestrous and breeding season. In anestrus, they become more responsive to inhibition by estradiol and thus likely contribute to the annual changes in estradiol negative feedback that drive seasonal reproduction in ewes. During the breeding season, when estradiol suppresses LH pulse amplitude and progesterone inhibits pulse frequency, kisspeptin mRNA expression in the ARC correlates with estradiol inhibition of pulse amplitude. Progesterone has no effect on kisspeptin mRNA expression suggesting that kisspeptin is not critical for progesterone negative feedback. This conclusion is consistent with previous data indicating that progesterone most likely inhibits LH pulse frequency via dynorphin produced in these same ARC neurons. Based on these data, we propose that one subpopulation of ARC neurons mediate the negative feedback actions of estradiol and progesterone, but do so via different neurotransmitters. Thus ARC kisspeptin neurons appear to be key mediators of steroid negative feedback in ewes; we are currently exploring the possibility that they are also involved in the positive feedback action of estradiol.