CYP7B1 enzyme deletion impairs reproductive behaviors in male mice

Mario G. Oyola, Damian G. Zuloaga, David Carbone, Anna M. Malysz, Alexandra Acevedo-Rodriguez, Robert J Handa, Shaila K. Mani

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2150-2161
Number of pages12
JournalEndocrinology
Volume156
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Reproductive Behavior
Dihydrotestosterone
Androgen Receptors
Enzymes
Androstane-3,17-diol
Anxiety
Genotype
Light
Ejaculation
Exploratory Behavior
Olfactory Bulb
Estrus
Corticosterone
Estrogen Receptors
Cues
Phenotype
Messenger RNA
Mutation
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Oyola, M. G., Zuloaga, D. G., Carbone, D., Malysz, A. M., Acevedo-Rodriguez, A., Handa, R. J., & Mani, S. K. (2015). CYP7B1 enzyme deletion impairs reproductive behaviors in male mice. Endocrinology, 156(6), 2150-2161. https://doi.org/10.1210/en.2014-1786

CYP7B1 enzyme deletion impairs reproductive behaviors in male mice. / Oyola, Mario G.; Zuloaga, Damian G.; Carbone, David; Malysz, Anna M.; Acevedo-Rodriguez, Alexandra; Handa, Robert J; Mani, Shaila K.

In: Endocrinology, Vol. 156, No. 6, 01.06.2015, p. 2150-2161.

Research output: Contribution to journalArticle

Oyola, MG, Zuloaga, DG, Carbone, D, Malysz, AM, Acevedo-Rodriguez, A, Handa, RJ & Mani, SK 2015, 'CYP7B1 enzyme deletion impairs reproductive behaviors in male mice', Endocrinology, vol. 156, no. 6, pp. 2150-2161. https://doi.org/10.1210/en.2014-1786
Oyola MG, Zuloaga DG, Carbone D, Malysz AM, Acevedo-Rodriguez A, Handa RJ et al. CYP7B1 enzyme deletion impairs reproductive behaviors in male mice. Endocrinology. 2015 Jun 1;156(6):2150-2161. https://doi.org/10.1210/en.2014-1786
Oyola, Mario G. ; Zuloaga, Damian G. ; Carbone, David ; Malysz, Anna M. ; Acevedo-Rodriguez, Alexandra ; Handa, Robert J ; Mani, Shaila K. / CYP7B1 enzyme deletion impairs reproductive behaviors in male mice. In: Endocrinology. 2015 ; Vol. 156, No. 6. pp. 2150-2161.
@article{8d47470ce6b941a5a6e725eb982e10d8,
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.",
author = "Oyola, {Mario G.} and Zuloaga, {Damian G.} and David Carbone and Malysz, {Anna M.} and Alexandra Acevedo-Rodriguez and Handa, {Robert J} and Mani, {Shaila K.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1210/en.2014-1786",
language = "English (US)",
volume = "156",
pages = "2150--2161",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - CYP7B1 enzyme deletion impairs reproductive behaviors in male mice

AU - Oyola, Mario G.

AU - Zuloaga, Damian G.

AU - Carbone, David

AU - Malysz, Anna M.

AU - Acevedo-Rodriguez, Alexandra

AU - Handa, Robert J

AU - Mani, Shaila K.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84930444203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930444203&partnerID=8YFLogxK

U2 - 10.1210/en.2014-1786

DO - 10.1210/en.2014-1786

M3 - Article

VL - 156

SP - 2150

EP - 2161

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 6

ER -