Progesterone and 3alpha,5alpha-THP enhance sexual receptivity in mice

Progesterone (P) and its metabolites' effects on sexual receptivity (lordosis) of mice was examined. P dosages that produced normal circulating concentrations of P and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) enhanced lordosis of ovariectomized, sexually experienced C57BL/6J (C57), +/+ C57BL/6Jx129SvEv (C57x129), and -/- C57BL/6Jx129SvEv (PRKO) mice. Only C57 and C57x129 mice had increases in progestin receptor (PR)-immunoreactivity (PR-IR) in the hypothalamus. RU38486, a PR antagonist, attenuated lordosis of C57 and C57x129, but not PRKO, mice; epostane, a progestin biosynthesis inhibitor, reduced plasma progestins; and finasteride, a P metabolism inhibitor, reduced plasma 3alpha,5alpha-THP and attenuated lordosis of all mice. For sexually naive mice, greater lordosis on initial sexual experience corresponded to greater concentrations of plasma and central progestins and increased central binding of a GABAA agonist, muscimol, compared with that seen in mice with lower lordosis on initial mating. Thus, P-facilitated receptivity in mice involves P and 3alpha,5alpha-THP and their actions at PRs and GABAA receptors.