Comparative analysis of GnRH pulse generator activity in intact and gonadectomized male and female mice

A subpopulation of kisspeptin neurons in the arcuate nucleus (ARN) of the hypothalamus functions as the GnRH pulse generator, driving the pulsatile secretion of LH from the anterior pituitary. Recent advances in in vivo GCaMP fiber photometry have allowed the direct measurement of ARN kisspeptin (ARNKISS) neuronal population activity in mice. In both sexes, ARNKISS neurons display large, brief calcium activity episodes, termed synchronization episodes, each corresponding to a correlated LH pulse. Here we present quantitative and comparative analyses of calcium activity in these neurons and LH profiles in male and female mice, based on a combination of previously published and unpublished data.

Our findings reveal a significant sex difference in pulse generator frequency in intact mice, with males exhibiting slower and more stochastic synchronization episodes compared to females. Additional sex differences were noted in the profile of synchronization episodes. In gonadectomized mice, the synchronization frequency and the episode profiles became similar across sexes, indicating that gonadal steroids largely drive sex differences in the intact state. However, sex-specific differences in pulse frequency distributions persisted after gonadectomy, suggesting possible steroid-independent differences in the GnRH pulse generator. Sex differences in the LH pulse frequency and amplitude were observed in intact mice and were abolished following gonadectomy, highlighting the correlation between synchronization episodes and downstream hormonal signaling.