Progesterone has rapid and membrane effects in the facilitation of female mouse sexual behavior

Ovariectomized (ovx) mice require both estradiol (E-2) and progesterone (P) administration to reinstate feminine sexual behavior (lordosis). The importance of P's actions at E-2-induced intracellular progestin receptors (PRs) to facilitate lordosis was investigated in PR knockout (PRKO) mice, PRKO's wild type littermates (C57x129), and wild type C57BL/6J (C57) mice. Subjects were ovx, E-2-primed (0.5 mu g) and tested following intravenous (i.v.) and intercereberal P. Intravenous P (200 mu g) significantly increased lordosis of all mice within 10 min of P, but vehicle infusion did not (Experiment 1). Intravenous P significantly increased the amount and duration and reduced the latency of lordosis, over that seen with vehicle infusion, in PRKO and wild type mice. Whole brain concentrations of P and its Se-reduced metabolite, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), which has low affinity for intracellular PRs, were also increased following P compared to vehicle infusion. Progesterone, but not vehicle infusions, significantly increased the number of PR-immunoreactive (PR-IR) cells in the ventromedial hypothalamus (VMH) of C57 and C57x129 mice and increased number of 3 alpha,5 alpha-THP-immunoreactive (3 alpha,5 alpha-THP-IR) cells in the ventral tegmental area (VTA) of all mice. In Experiment 2, P conjugated to bovine serum albumin (P:BSA) increased lordosis when applied bilaterally to both the VMH and VTA of E-2-primed mice more than BSA implants. Progesterone implants increased the number of PR-IR cells in the VMH of C57 and C57x129 mice and the number of 3 alpha,5 alpha-THP-IR cells in the VTA of all mice. The rapid facilitation of lordosis with i.v. P infusion and increases in lordosis when P's effects are relegated to the membrane in the VMH and VTA of PRKO and wild type mice suggest that P may facilitate lordosis through actions at substrates other than intracellular PRs. The present findings suggest a role of 3 alpha,5 alpha-THP. (C) 1999 Elsevier Science B.V. AU rights reserved.