State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Endocrinology. 2010 Feb;151(2):774-82. doi: 10.1210/en.2009-0751. Epub 2009 Dec 23.
Increasing evidence has shown that excess androgen may be a main cause of polycystic ovary syndrome (PCOS). However, the molecular mechanism of androgen action on the ovary is unclear. To investigate the possible impacts of androgen on early follicular development, neonatal mouse ovaries mainly containing primordial follicles were cultured with testosterone. We demonstrated that the number of primary follicles was increased after 10 d culture with testosterone treatment via phosphatidylinositol 3-kinase/Akt pathway. Androgen induced Forkhead box (Foxo)-3a activation, and translocation of Foxo3a protein from oocyte nuclei to cytoplasm, which might be a key step for primordial follicle activation. Interestingly, testosterone was also capable of down-regulating growth and differentiation factor-9 expression via its receptor. In summary, we infer that intraovarian excess androgen in PCOS might result in excess early follicles by inducing oocyte Foxo3a translocation and follicular arrest by down-regulating growth and differentiation factor-9 expression.
越来越多的证据表明，过量的雄激素可能是多囊卵巢综合征（PCOS）的主要原因。然而，雄激素在卵巢中的作用的分子机制尚不清楚。为了研究雄激素对早期卵泡发育的可能影响，我们用睾酮培养新生小鼠卵巢，其中主要含有原始卵泡。我们通过磷酸肌醇 3-激酶/ Akt 途径证明，用睾酮处理 10 天后，初级卵泡的数量增加。雄激素诱导叉头框（Foxo）-3a 激活，Foxo3a 蛋白从卵母细胞核转位到细胞质，这可能是原始卵泡激活的关键步骤。有趣的是，睾酮也能够通过其受体下调生长分化因子-9 的表达。总之，我们推断 PCOS 中卵巢内过量的雄激素可能通过诱导卵母细胞 Foxo3a 易位，并通过下调生长分化因子-9 的表达使卵泡停滞，从而导致早期卵泡过多。
