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