GENOMIC AND NON-GENOMIC ACTIONS OF PROGESTERONE IN THE CONTROL OF FEMALE HAMSTER SEXUAL-BEHAVIOR

Genomic Progesterone (P) in both the ventromedial hypothalamus (VMH) and the ventral tegmental area (VTA) is necessary to facilitate sexual receptivity in estrogen-primed hamsters. The mechanism of P may be different in the VMH and VTA, as there are many intracellular progestin receptors (PR) in the VMH but few in the VTA. Progesterone conjugated to bovine serum albumin (P-3-BSA) does not bind well to intracellular PR or permeate the surface of neuronal membranes. However, VTA application of P-3-BSA rapidly increases sexual receptivity if P has been applied earlier to the VMH. P-S-BSA is ineffective when applied to the VMH. The membrane-limited effect of P may be related to the ability of some progestins to modulate the GABA(A)-benzodiazepine receptor complex (GBRC). We have found that infusions of a GABA(A) agonist, muscimol, into the VTA enhance and a GABA(A) antagonist, bicuculline, inhibit receptivity. Because P itself is not highly effective at the GBRC, and since the most potent modulators of the GBRC, the 5 alpha-reduced progestins, do not bind well to PRs, progestin metabolites were applied to the VTA. Only the potent GBRC modulators facilitated sexual receptivity when applied to the VTA concurrent with P to the VMH. The reverse treatment, with a progestin metabolite implanted into the VMH, was ineffective. VTA infusions of an inhibitor of 5 alpha-reductase also attenuated behavioral estrus in hamsters. These data are consistent with P facilitation of sexual receptivity being genomically mediated in the VMH, while the non-genomic actions of P in the VTA may be a result of metabolism and subsequent interaction with the GBRC. (C) 1994 Academic Press, Inc.