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

Brain Res. 1999 Jan 9;815(2):259-69. doi: 10.1016/s0006-8993(98)01132-9.


Ovariectomized (ovx) mice require both estradiol (E2) and progesterone (P) administration to reinstate feminine sexual behavior (lordosis). The importance of P's actions at E2-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, E2-primed (0.5 microg) and tested following intravenous (i. v.) and intercereberal P. Intravenous P (200 microg) 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 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-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 3alpha, 5alpha-THP-immunoreactive (3alpha,5alpha-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 E2-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 3alpha,5alpha-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 3alpha,5alpha-THP.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Membrane / drug effects
  • Estradiol / administration & dosage
  • Female
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Posture / physiology
  • Pregnanolone / physiology
  • Progesterone / administration & dosage*
  • Progesterone / blood
  • Sexual Behavior, Animal / drug effects*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • Ventromedial Hypothalamic Nucleus / drug effects
  • Ventromedial Hypothalamic Nucleus / metabolism


  • Progesterone
  • Estradiol
  • Pregnanolone