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The BMP4-Smad signaling pathway regulates hyperandrogenism development in a female mouse model.

ABSTRACT: Polycystic ovary syndrome is a common endocrine disorder and a major cause of anovulatory sterility in women at reproductive age. Most patients with polycystic ovary syndrome have hyperandrogenism, caused by excess androgen synthesis. Bone morphogenetic protein 4 (BMP4) is an essential regulator of embryonic development and organ formation, and recent studies have also shown that BMP4 may be involved in female steroidogenesis process. However, the effect of BMP4 on hyperandrogenism remains unknown. Here, using a female mouse model of hyperandrogenism, we found that ovarian BMP4 levels were significantly decreased in hyperandrogenism. Elevated androgens inhibited BMP4 expression via activation of androgen receptors. Moreover, BMP4 treatment suppressed androgen synthesis in theca cells and promoted estrogen production in granulosa cells by regulating the expression of steroidogenic enzymes, including CYP11A, HSD3B2, CYP17A1, and CYP19A1 Consistently, knockdown of BMP4 augmented androgen levels and inhibited estrogen levels. Mechanistically, Smad signaling rather than the p38 MAPK pathway regulated androgen and estrogen formation, thereby mediating the effect of BMP4. Of note, BMP4-transgenic mice were protected against hyperandrogenism. Our observations clarify a vital role of BMP4 in controlling sex hormone levels and offer new insights into intervention for managing hyperandrogenism by targeting the BMP4-Smad signaling pathway.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5512069 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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The BMP4-Smad signaling pathway regulates hyperandrogenism development in a female mouse model.

Liu Yang Y Du Shao-Yue SY Ding Meng M Dou Xin X Zhang Fei-Fei FF Wu Zhi-Yong ZY Qian Shu-Wen SW Zhang Wei W Tang Qi-Qun QQ Xu Cong-Jian CJ

The Journal of biological chemistry 20170601 28

Polycystic ovary syndrome is a common endocrine disorder and a major cause of anovulatory sterility in women at reproductive age. Most patients with polycystic ovary syndrome have hyperandrogenism, caused by excess androgen synthesis. Bone morphogenetic protein 4 (BMP4) is an essential regulator of embryonic development and organ formation, and recent studies have also shown that BMP4 may be involved in female steroidogenesis process. However, the effect of BMP4 on hyperandrogenism remains unkno ...[more]

PMID: 28572510

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The BMP4-Smad signaling pathway regulates hyperandrogenism development in a female mouse model.

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The BMP4-Smad signaling pathway regulates hyperandrogenism development in a female mouse model.

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