Conditional Knockout of the Androgen Receptor in Ovarian Theca Cells Reveals Altered Steroidogenesis in Aged Mice

Abstract

Women with polycystic ovary syndrome (PCOS) exhibit symptoms of hyperandrogenism, oligo/amenorrhea and polycystic ovaries. PCOS is also commonly associated with metabolic syndrome, hyperinsulimia, and insulin resistance in metabolic tissues. It has been reported that elevated androgen levels in women can lead to infertility; however the target organs impacted by the elevated androgen levels are not yet fully known. The aims of the study were to determine the role of androgen signaling in the ovary on the development and reproductive function. Our model system used the cre‐lox system to generate ovarian theca specific androgen receptor knockout (ThARKO) mice. This study examined puberty, cyclicity and fertility in female mice. There was no difference in the age of puberty between control and ThARKO littermates, assessed by the age of vaginal opening and first estrus. Cyclicity and fertility were also studied, and there were no significant differences between control and ThARKO mice. Ovarian gene expression and fertility were compared between 3 months old mice and 8 months old mice. We observed decreased cyp19 (aromatase) mRNA levels in both 3 and 8 moths old groups of the ThARKO compared to control littermates. However, cyp17 (rate limiting enzyme for androgen synthesis) mRNA expression was only significantly reduced (P<0.05) in 8 months old ThARKO mice compared to control littermates. Although fertility was not altered in ThARKO mice, the AR in theca cells may play a role in steroidogenesis of aged mice.