title: Female mice with deletion of Type One 5α-reductase have reduced reproductive responding during proestrus and after hormone-priming.
abstract: The capacity to form progesterone (P₄)'s 5α-reduced metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP; a.k.a. allopregnanolone), in the brain may be related to facilitation of lordosis among estrogen-primed (E₂) mice. We investigated this idea further by comparing effects of endogenous and exogenous progestogens in mice that are deficient in the Type One 5α-reductase enzyme (5α-reductase knockout mice; 5α-RKO), and their wildtype counterparts for sexual behavior. Comparisons were made following administration of progestogens that are expected to increase 3α,5α-THP or not. Sexual receptivity of 5α-RKO mice and their wildtype counterparts was examined when mice were naturally-cycling (Experiment 1); ovariectomized (OVX), E₂-primed (10 μg, subcutaneous; SC) and administered P₄ (0, 125, 250, or 500 μg SC; Experiment 2); and OVX, E₂-primed and administered P₄, medroxyprogesterone acetate (MPA, 4 mg/kg, SC, which does not convert to 3α,5α-THP) or 3α,5α-THP (4 mg/kg, SC; Experiment 3). The percentage of mounts that elicited lordosis (lordosis quotient) or aggression/rejection behavior (aggression quotient), as well as the quality of lordosis (lordosis rating), was scored. Wildtype, but not 5α-RKO, mice in behavioral estrus demonstrated significantly greater lordosis quotients and lordosis ratings, but similar aggression quotients, compared to their diestrous counterparts. Among OVX and E₂-primed mice, P₄ facilitated lordosis of wildtype, but not 5α-RKO, mice. MPA neither facilitated lordosis of wildtype, nor 5α-RKO mice. 3α,5α-THP administered to wildtype or 5α-RKO mice increased lordosis quotients and lordosis ratings and decreased aggression quotients. 3α,5α-THP levels in the midbrain, one brain region important for sexual behavior, were increased during behavioral estrus, with P4 administered to WT, but not 5α-RKO mice, and 3α,5α-THP administered to WT and 5α-RKO mice. MPA did not increase 3α,5α-THP. Thus, deletion of Type One 5α-reductase among female mice may attenuate reproductive responding during the estrous cycle and after hormone-priming.
authors.affiliation: Department of Psychology, University at Albany-SUNY, Albany, NY, United States; Institute of Arctic Biology, University of Alaska-Fairbanks, Fairbanks, AK, United States; IDeA Network of Biomedical Excellence (INBRE), University of Alaska-Fairbanks, Fairbanks, AK, United States.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Koonce
authors.affiliation: Department of Psychology, University at Albany-SUNY, Albany, NY, United States; Department of Biological Sciences, University at Albany-SUNY, Albany, NY, United States; The Centers for Neuroscience and Life Sciences Research, University at Albany-SUNY, Albany, NY, United States; Department of Chemistry & Biochemistry, University of Alaska-Fairbanks, Fairbanks, AK, United States; Institute of Arctic Biology, University of Alaska-Fairbanks, Fairbanks, AK, United States; IDeA Network of Biomedical Excellence (INBRE), University of Alaska-Fairbanks, Fairbanks, AK, United States. Electronic address: cafrye@alaska.edu.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Frye
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase / Q000172:deficiency*; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D011359:Proestrus / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D011374:Progesterone; D042944:Cholestenone 5 alpha-Reductase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C518406:Srd5a1 protein, mouse
keywords: Allopregnanolone; Lordosis; Medroxyprogesterone acetate; Midbrain; Sexual behavior