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Psychoneuroendocrinology

Title:		Steroid 5alpha-reductase 2 deficiency leads to reduced dominance-related and impulse-control behaviors
Author(s):		Mosher LJ; Godar SC; Morissette M; McFarlin KM; Scheggi S; Gambarana C; Fowler SC; Di Paolo T; Bortolato M;
Address:		"Dept of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States; Dept of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, United States. Dept of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States. Neuroscience Research Unit, Centre Hospitalier Universitaire de Quebec, CHUL, Quebec City, Quebec, Canada. Dept of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, United States. Electronic address: kennethmcfarlin@ku.edu. Dept of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Dept of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, United States. Neuroscience Research Unit, Centre Hospitalier Universitaire de Quebec, CHUL, Quebec City, Quebec, Canada; Faculty of Pharmacy, Laval University, Quebec City, Quebec, Canada. Dept of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States. Electronic address: marco.bortolato@utah.edu"
Journal Title:		Psychoneuroendocrinology
Year:		2018
Volume:		20180216
Issue:
Page Number:		95 - 104
DOI:		10.1016/j.psyneuen.2018.02.007
ISSN/ISBN:		1873-3360 (Electronic) 0306-4530 (Print) 0306-4530 (Linking)
Abstract:		"The enzyme steroid 5alpha-reductase 2 (5alphaR2) catalyzes the conversion of testosterone into the potent androgen 5alpha-dihydrotestosterone. Previous investigations showed that 5alphaR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5alphaR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5alphaR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses. Furthermore, male 5alphaR2 KO mice exhibited reduced D(2)-like dopamine receptor binding in the shell of the nucleus accumbens - a well-recognized molecular signature of social dominance. Collectively, these results suggest that 5alphaR2 is involved in the establishment of social dominance and its behavioral manifestations. Further studies are warranted to understand how the metabolic actions of 5alphaR2 on steroid profile may be implicated in social ranking, impulse control, and the modulation of dopamine receptor expression in the nucleus accumbens"
Keywords:		"3-Oxo-5-alpha-Steroid 4-Dehydrogenase/*deficiency/metabolism/*physiology Androgens/metabolism Animals Behavior, Animal/*physiology Dihydrotestosterone/metabolism Disorder of Sex Development, 46, XY/psychology Disruptive, Impulse Control, and Conduct Disord;Neuroscience;"
Notes:		"MedlineMosher, Laura J Godar, Sean C Morissette, Marc McFarlin, Kenneth M Scheggi, Simona Gambarana, Carla Fowler, Stephen C Di Paolo, Therese Bortolato, Marco eng F31 NS093939/NS/NINDS NIH HHS/ R01 MH104603/MH/NIMH NIH HHS/ R21 HD070611/HD/NICHD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2018/03/16 Psychoneuroendocrinology. 2018 May; 91:95-104. doi: 10.1016/j.psyneuen.2018.02.007. Epub 2018 Feb 16"