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

AUTOR(ES)

Omoto, Yoko

FONTE

National Academy of Sciences

RESUMO

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.

Documentos Relacionados

• Digenic Inheritance of Early-Onset Glaucoma: CYP1B1, a Potential Modifier Gene
• Leptin accelerates the onset of puberty in normal female mice.
• Acceleration of puberty onset in female mice by male urinary proteins.
• BRCA1 and BRCA2 mutation analysis in 86 early onset breast/ovarian cancer patients.
• Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin