Endocrine Abstracts

In mammals, the preovulatory LH surge is thought to be triggered by enhanced release of GnRH into the hypothalamic–pituitary portal blood vessels. Recently, we discovered that the medial basal hypothalamus (MBH) of rhesus macaques (Macaca mulatta) contains two distinct populations of GnRH-producing neurones. One of these populations expresses the traditional mammalian form of GnRH (i.e. GnRH-I) while the other expresses a more conserved vertebrate form of GnRH (i.e. GnRH-II). Using various molecular biology approaches (i.e. in situ hybridization histochemistry, RT-PCR, gene microarrays and real-time PCR), we have found that oestradiol differentially affects GnRH-I and GnRH-II gene expression in the female monkey MBH, causing a suppression of the former and a stimulation of the latter. This leads us to hypothesize that the GnRH-II producing neurones play a primary role in mediating the positive feedback action of oestrogen on the preovulatory LH surge, whereas the GnRH-I neurones play a more permissive role. To test this hypothesis, we performed an additional experiment, in which oestradiol benzoate (EB) was administered to a group of ovariectomized adult rhesus macaques. We evaluated the response by measuring serum oestradiol and LH concentrations, and examining GnRH-I and GnRH-II mRNA levels in the MBH. As expected, EB induced an LH surge ~48 h later. Importantly, this surge coincided closely with a marked increase in the expression of GnRH-II, but not GnRH-I, confirming the stimulatory influence of oestrogen on the GnRH-II neurones. Because humans also express two forms of GnRH (i.e. GnRH-I and GnRH-II), it is plausible that fertility in women is regulated by the coordinated action of two distinct GnRH neuronal populations, which are differentially affected by the sex-steroid environment. Supported by NIH Grants: HD-29186 & RR-00163, and approved by the Institutional Animal Care and Use Committee.