Session: S17-Keeping a Finger on Pulse Generation
Room 206 (Moscone Center)
Pulsatile GnRH release is controlled by synaptic inputs, such as kisspeptin neurons. Our recent studies, however, suggest that neuroestradiol, synthesized and released in the hypothalamus, appears to play a role in modulating GnRH pulsatility. We first examined whether a brief infusion of estradiol benzoate (E2B) into the medial basal hypothalamus of ovariectomized monkeys induces excitatory E2 effects in vivo using a microdialysis method. Results indicate that E2B (10-100 nM) stimulated a rapid increase in GnRH release followed by pulsatile E2 release, measured by LC/MS. Surprisingly, the E2B induced-E2 release was as high as circulating preovulatory E2 levels. Electrical stimulation of the MBH also stimulated GnRH release followed by E2 release. Moreover, infusion of the aromatase inhibitor, letrozole, into the MBH suppressed spontaneous GnRH pulses as well as the E2B-induced release of GnRH and E2. These findings suggest that neuroestradiol plays a role similar to a neurotransmitter, regulating pulsatile GnRH release.