title: Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5α-reductase Type 1 mutant, mice.
abstract: Progesterone (P4) facilitates exploration, anxiety and social behaviors in estrogen (E2)-primed mice. Some of these effects may be due to actions of its 5α-reduced metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP). In order to address the role of P4 and its metabolite, 3α,5α-THP, a mouse model was utilized. We hypothesized that if P4's metabolism to 3α,5α-THP is essential to facilitate exploratory, anti-anxiety and social behaviors of mice, then wildtype, but not 5α-reductase knockout (5α-RKO), mice will have greater expression of these behaviors. Experiment 1: Mice were ovariectomized (ovx), E2-primed and administered P4 (0, 125, 250, or 500μg) subcutaneously and then tested 4h later in a battery of tasks: open field, elevated plus maze, and social interaction. Experiment 2: Ovx, E2-primed mice were administered P4 (4mg/kg), 3α,5α-THP (4mg/kg), medroxyprogesterone acetate (MPA, which does not convert to 3α,5α-THP; 4mg/kg), or vehicle subcutaneously and tested 4h later. There was a dose-dependent effect of P4 to wildtype, but not 5α-RKO, mice. Neither wildtype, nor 5α-RKO, mice had increased exploration, anti-anxiety or pro-social behavior with MPA administration. Progesterone only exerted effects on anti-anxiety behavior, and increased 3α,5α-THP in the prefrontal cortex and hippocampus, when administered to wildtype mice. 3α,5α-THP to both WT and 5α-RKO mice increased exploration, anti-anxiety and social interaction and 3α,5α-THP levels in the hippocampus and prefrontal cortex. Thus, metabolism of P4 by the 5α-reductase enzyme may be essential for enhancement of these behaviors.
authors.affiliation: Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Koonce
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Frye
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000502:physiology*; D000339:Affect / Q000187:drug effects*; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D007398:Interpersonal Relations; D008525:Medroxyprogesterone / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation / Q000502:physiology*; D010052:Ovariectomy; D011280:Pregnanolone / Q000031:analogs & derivatives / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D012919:Social Behavior; D013256:Steroids / Q000378:metabolism
chemical_list: D013256:Steroids; D011374:Progesterone; C051190:pregnan-3,6-diol-20-one; D011280:Pregnanolone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D008525:Medroxyprogesterone
keywords: 3α,5α-THP; Hippocampus; Medroxyprogesterone acetate; Neurosteroid; Prefrontal cortex