title: Progesterone has rapid and membrane effects in the facilitation of female mouse sexual behavior.
abstract: 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.
authors.affiliation: Department of Psychology, SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.cafrye@cnsunix.albany.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Frye
authors.forename: J M
authors.initials: JM
authors.lastname: Vongher
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011187:Posture / Q000502:physiology; D011280:Pregnanolone / Q000502:physiology; D011374:Progesterone / Q000008:administration & dosage* / Q000097:blood; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D011374:Progesterone; D004958:Estradiol; D011280:Pregnanolone