SUN-035 A Role for GNRH-II in the Control of Puberty?

Abstract

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons represent the primary neuroendocrine link between the brain and the reproductive system. Although they play a key role in stimulating the release of FSH and LH from the anterior pituitary gland, the underlying mechanism by which they trigger the onset of puberty is unclear. To address this issue, RT-PCR, in situ hybridization histochemistry, and Affymetrix gene arrays were used to profile hypothalamic GnRH gene expression in prepubertal and adult rhesus macaques (Macaca mulatta). Like humans, these nonhuman primates express two molecular forms of GnRH (GnRH-I and GnRH-II), both of which are highly effective at stimulating gonadotropin release via the same GnRHR1 receptor. However, only GnRH-II shows increased hypothalamic expression in the presence of elevated estrogen concentrations (i.e., positive feedback), whereas GnRH-I expression either remains the same or decreases (i.e., negative feedback). In the present study, the hypothalamic expression levels of GnRH-I and GnRHR1 were found to be no different between prepubertal and adult animals, despite marked differences in circulating sex-steroid hormone levels, whereas the hypothalamic expression level of GnRH-II was significantly higher in the adults than in the juveniles. Therefore, although the traditional GnRH-I neurons are likely to play a fundamental role in initiating FSH and LH release during the early stages of pubertal development, GnRH-II neurons may play an important role in maintaining elevated gonadotropin release during the final stages (i.e., at a time when the GnRH-I neurons are subjected to increasing negative sex-steroid feedback from the maturing gonads). Taken together, the data suggest that sexual maturation in primates is likely to be orchestrated by the concerted action of two distinct GnRH neuronal subtypes that respond differentially to sex-steroid feedback.