Progesterone and the neural mechanisms of hamster sexual behavior.

Stimulation of both the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) by progesterone is necessary to facilitate sexual behavior in female hamsters. Recently obtained evidence indicates that progesterone exerts its behaviorally relevant actions in the VTA by acting on cell membranes. When progesterone conjugated to bovine serum albumin, which cannot permeate the cell membrane, is applied to the VTA concurrent with free progesterone to the VMH, estrogen-primed hamsters become sexually receptive. Since the reverse treatment is ineffective, this suggests that progesterone's nongenomic effects in the VTA may require concurrent genomic activation by progesterone in the VMH. The nongenomic action of progesterone on sexual receptivity may involve the GABAA receptor complex, as progestins are known to modulate this receptor complex. VTA infusions of GABAA agonists enhance, and antagonists inhibit, progesterone's effectiveness on receptivity. Finally, the behavioral effectiveness of progesterone metabolites in the VTA, concurrent with progesterone in the VMH, is consistent with their relative biochemical efficacy at the GABAA complex. These data suggest that progesterone may exert its behavioral effects in the VTA through GABAA. However, it is not yet clear whether progesterone normally acts directly on GABAA in the VTA. Progesterone may also act at some other membrane binding site and GABAA may represent an indirect mechanism for progesterone.