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Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2814-9. Epub 2005 Feb 14.

Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

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1
Department of Medical Nutrition, Karolinska Institute, 141 86 Huddinge, Sweden.

Erratum in

  • Proc Natl Acad Sci U S A. 2006 May 23;103(21):8298.

Abstract

CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

PMID:
15710898
PMCID:
PMC549492
DOI:
10.1073/pnas.0500198102
[Indexed for MEDLINE]
Free PMC Article
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