CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice.

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TitleCYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice.
Publication TypeJournal Article
Year of Publication2015
AuthorsOyola, MG, Zuloaga, DG, Carbone, D, Malysz, AM, Acevedo-Rodriguez, A, Handa, RJ, Mani, SK
Date Published2015 Jun
KeywordsAnimals, Anxiety, Calbindins, Cytochrome P450 Family 7, Female, Immunohistochemistry, Male, Mice, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Sexual Behavior, Animal, Steroid Hydroxylases

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.

Alternate JournalEndocrinology
PubMed ID25849728
PubMed Central IDPMC4430609
Grant ListR01 HD062512 / HD / NICHD NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
P30 HD024064 / HD / NICHD NIH HHS / United States
R01 NS039951 / NS / NINDS NIH HHS / United States
5P30HD024064 / HD / NICHD NIH HHS / United States