title: CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice.
abstract: In addition to androgenic properties mediated via androgen receptors, dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate pathway. These estrogenic functions of DHT are mediated by its metabolite 5α-androstane-3β, 17β-diol (3β-diol) binding to estrogen receptor β (ERβ). CYP7B1 enzyme converts 3β-diol to inactive 6α- or 7α-triols and plays an important role as a regulator of estrogenic functions mediated by 3β-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene (CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior. Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were assessed for their behavioral phenotype, anxiety-related behavioral measures, and hypothalamic pituitary adrenal axis reactivity. No significant effects of genotype were evident in anxiety-like behaviors in open field (OFA), light-dark (L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO and WT littermates. T also attenuated the corticosterone response to EPM in both genotypes. In GDX animals, T was able to reinstate male-specific reproductive behaviors (latencies and number of mounts, intromission, and ejaculations) in the WT but not in the CYP7B1KO mice. The male reproductive behavior defect in CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role for the CYP7B1 enzyme in the regulation of male reproductive behaviors.
authors: Department of Neuroscience (M.G.O., A.A.-R., S.K.M.), Molecular & Cellular Biology (A.M.M., S.K.M.), Memory and Brain Research Center (M.G.O., A.M.M., A.A.-R., S.K.M.), Baylor College of Medicine, Houston, Texas 77030; and Department Of Basic Medical Sciences (D.G.Z., D.C., R.J.H.), University of Arizona College of Medicine, Phoenix, Arizona 85004.
authors: Mario G
authors: MG
authors: Oyola
authors: Damian G
authors: DG
authors: Zuloaga
authors: David
authors: D
authors: Carbone
authors: Anna M
authors: AM
authors: Malysz
authors: Alexandra
authors: A
authors: Acevedo-Rodriguez
authors: Robert J
authors: RJ
authors: Handa
authors: Shaila K
authors: SK
authors: Mani
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D064026:Calbindins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000072474:Cytochrome P450 Family 7; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012726:Sexual Behavior, Animal / Q000502:physiology*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D064026:Calbindins; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C097207:Cyp7b1 protein, mouse