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Androgen Receptor May Be Key to Premature Ovarian Failure

In mouse study, androgen receptor appears to control development of ovarian follicles

THURSDAY, Dec. 22 (HealthDay News) -- Genetically engineered mice that lack androgen receptors develop premature ovarian failure (POF), according to a study published online Dec. 21 in the Proceedings of the National Academy of Sciences Early Edition. The finding suggests that POF in women could be related to androgen signaling irregularities, or to inherited disruptions in the androgen receptor gene, which is located on the X chromosome.

POF syndrome leads to infertility and cessation of menstruation before the age of 40. Such patients often have X-chromosome abnormalities, although the gene responsible is unknown.

Shigeaki Kato, Ph.D., of the University of Tokyo, Japan, and colleagues disrupted the function of the androgen receptor gene in mice. Although the female knockout mice were initially fertile, at eight weeks of age they had fewer ovarian follicles, impaired mammary development and produced only half the normal number of pups per litter. By 40 weeks of age, the mice lost all their follicles and were completely infertile.

The researchers then examined gene expression in ovaries from normal and knockout mice and found that the androgen receptor controlled the expression of many genes involved in folliculogenesis. "From a clinical perspective, the present study provides evidence that androgen receptor can be a beneficial therapeutic target in treatment of POF syndrome patients," Kato and colleagues conclude.

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