Endocrine Abstracts (2012) 28 P283

Androgens stimulate growth of mouse preantral follicles in culture

Jennifer Connolly, Tina Tremaine, Jossie Mora, Mark Fenwick, Kate Hardy & Stephen Franks

Institute of Reproductive & Developmental Biology, Imperial College London, London, United Kingdom.

Polycystic ovary syndrome is the commonest cause of anovulation. The mechanism of the aberrant follicle development that is associated with anovulation remains unclear. However, data from human studies and from animal models of PCOS suggest that excess androgen production, the biochemical hallmark of PCOS, has a role in disordered follicle development. The aim of this study was to examine the direct effect of androgens on isolated mouse preantral follicles in culture. Multilayered preantral follicles (90–120 microns in diameter) were mechanically isolated, using acupuncture needles, from juvenile C57BL/6 mice at PND12–14. Follicles were cultured individually in 96-well plates in supplemented αMEM medium for 96 h in the presence or absence of various doses of FSH, testosterone (T) and dihydrotestosterone (DHT). The effect of treatment on follicle growth and gene expression was examined. In histological sections of whole ovary, androgen receptor (AR) protein was abundantly expressed in granulosa cells of follicles at all stages of development. In the absence of FSH, mean follicle volume increased during culture by 40% by 96 h. Addition of DHT at all doses (1,10,100 nM) significantly augmented follicle growth compared with control medium (P<0.001, ANOVA), but there was no difference between doses. Testosterone (1–100 nM) also increased follicle volume compared with controls, but in a dose-dependent manner. As expected, FSH promoted a dose-dependent increase in follicle volume during culture. DHT (10 nM) together with FSH (1 or 3 ng/ml) produced a greater increase (P<0.0001) in follicle diameter than either DHT or FSH alone. DHT alone (10nM) did not affect AR gene expression (qPCR), but induced a 3-fold increase in FSH receptor mRNA (P<0.05). In conclusion, these data indicate that androgens have a direct stimulatory effect on follicle development, supporting the view that androgen has a direct role in the accelerated growth of preantral follicles observed in women with PCOS.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: MRC and BBSRC.

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