5α-reduced progesterone metabolites are essential in hamster VTA for sexual receptivity

Progesterone's (P) actions in the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) are essential for sexual receptivity in hamsters. This study investigates the notion that P works in the VTA in the absence of intracellular P receptors (PRs) by 5α-reduction to progestins, which would subsequently bind to membrane γ-Aminobutyric Acid receptor complexes (GBRs). To test the importance of P metabolism, a 5α-reductase inhibitor, 17β-N, N-diethylcarbamoyl-4-methyl-4aza-5α-androstan-3-one (4MA) was administered SC (0, 3, 9, 15, 24, or 30mg/kg) to ovx estradiol benzoate(EB)-primed hamsters, followed by one of six doses of SC P (0, 25, 50, 100, 200, or 500μg) and sexual receptivity testing. 200μg P-treated animals administered higher (24 and 30 mg/kg) doses of 4MA had significantly decreased total lordosis durations (TLDs) compared to 0 mg/kg 4MA controls (exp 1). In exp 2, 4MA was aimed bilaterally at the VTA prior to SC P. After 200μg P, animals had significantly lower TLDs than after 500μg P, 3 hours following bilateral VTA implantation of 4MA, but not cholesterol. In exp 3, cycling female hamsters were infused with 1.0μg 4MA or vehicle unilaterally into the VTA on diestrus, proestrus, and estrus. 4MA, but not vehicle, infusions into the VTA interrupted receptivity in estrus and proestrus animals, but had no effect on diestrus animals. 4MA's reduction of receptivity when given systematically and intracranially strongly supports the hypothesis that 5α-reduced P metabolites, possibly interacting with GBRs in the VTA, are essential for sexual receptivity in hamsters.