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

Yoko Omoto, Richard Lathe, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5α-androstane-3β, 17β-diol (3βAdiol). 3βAdiol is estrogenic in ERα or ERβ 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 3βAdiol, CYP7B1 performs two major tasks: (i) it allows 3βAdiol to have growth inhibitory effects through ERβ and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3βAdiol. When CYP7B1 is inactivated, 3βAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

Original languageEnglish (US)
Pages (from-to)2814-2819
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number8
DOIs
StatePublished - Feb 22 2005

Keywords

  • 3βAdiol
  • Cytochrome P-450
  • Estrogen receptor
  • Mammary gland
  • Precocious puberty

ASJC Scopus subject areas

  • Genetics
  • General

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