The applicant has shown that testosterone (T) acts on the brain to decrease gonadotropin releasing-hormone (GnRH) pulse frequency. The overall aim of the proposed studies is to test the general hypothesis that T suppresses GnRH pulse frequency in the male, in part, by acting at the medical preoptic area (mPOA) to increase secretion of gamma aminobutyric acid (GABA), and decrease secretion of glutamate and aspartate, excitatory amino acids (EAA).
The specific aims are: 1. To test the hypothesis that T exerts its inhibitory effect on GNRN pulse frequency by acting at the mPOA. This will be addressed by placing bilateral microimplants of the testosterone into the mPOA, the arcuate- ventromedial region (ARC-VMR), and both regions simultaneously, and then monitoring subsequent changes of LH pulse patterns in or chidectomized (ORCH) rams. 2. To test the hypothesis that GABA suppresses GnRH pulse frequency in the ram. This will be done by perfusing GABA agonists and antagonists into the mPOA and then monitoring changes of LH pulse patterns in ORCH and ORCH, T-treated rams. 3. To test the hypothesis that EAAs increase GnRH pulse frequency. This will be done by perfusing EAA agonists and antagonists into the mPOA of oRCH and T-treated ORCH rams and then monitoring changes in LH pulse frequency. 4. To test the hypothesis that T elevates GABA and reduces EAA secretion in the mPOA. This will be done by monitoring GABA and EAA release from the POA using push-pull cannule and simultaneously monitoring circulating LH in ORCH rams treated with T or diluent. 5. To test the null hypothesis that there is little coincidence between oscillations of GABA, and EAA secretion in the mPOA and of GnRH release. A longitudinal study of simultaneous temporal changes of GABA, EAA, GnRH, and LH secretion will be done in ORCH and ORCH + T-treated rams. These studies are important for understanding both control of the GnRH pulse-generating system and the action of T in regulating GnRH and LH secretion.
