Endocrinology & Metabolic Syndrome
Open Access

Alternative splicing of the androgen receptor in PCOS with ovulatory dysfunction

Polycystic Ovarian Syndrome Conference

November 16-18, 2015 Seattle, USA

Hefeng Huang

Shanghai Jiao Tong University School of Medicine, China

Posters-Accepted Abstracts: Endocrinol Metab Syndr

Abstract :

Androgen receptor is essential for healthy developing follicle, while excess intra-ovarian androgens impair follicle growth. Hyperandrogenism is main characteristic of polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder and major threat to womenâ��s health. However, the etiology of hyperandrogenism is poorly understood. We describe the specific transcription of two AR splice variants, insertion (ins) and deletion (del) isoforms, in granulosa cells (GCs) of women with PCOS. Wild-type (wt) AR existed in each individual; surprisingly its transcription is comparable between PCOS and control group. Women with AR ins or del isoforms showed distinct hyperandrogenism, attenuated androgen metabolism, enhanced androgen synthesis and altered expression corresponding enzymes, aromatase and steroid 17�±-hydroxylase, in GCs, particularly the former. In vitro over-expression of different AR variants in primarily cultured human GCs not only confirmed the in vivo results, but also revealed notable change of expression of folliculogenesis, steroidogenesis and ovarian structure modeling-related genes. Its underlying mechanism is inferior ability of nuclear shuttle and DNA binding, including U1 androgen response element (ARE) of CYP19A1 gene, of AR as nuclear receptor. In conclusion, alternative splicing of AR in GCs is a cause of hyperandrogenism, leading to follicular arrest in PCOS.

Biography :

Email: huanghefg@hotmail.com