Reproductive effects of irisin: Initial in vitro studies.

The recently discovered myo- and adipokine irisin affects insulin sensitivity in classical insulin target tissues (adipose tissue, skeletal muscle and liver), but the reproductive effects of this hormone, if any, remain largely unexplored. We hypothesized that irisin may have effects on the hypothalamic-pituitary-gonadal axis. To test this hypothesis, we used murine pituitary mPit12 and human ovarian granulosa cells. GnRH treatment resulted in significant (up to 2.5-fold, p<0.0005) and dose-dependent stimulation of LH production by the mPit12 cells. Treating these cells with irisin alone showed a significant stimulatory effect on LH synthesis only at irisin concentration of 100ng/ml. When used together with GnRH, irisin abolished the stimulatory effect of GnRH on LH production. Human ovarian granulosa cells were treated with insulin, irisin or a combination of both and the estradiol (E2) production was measured. Both insulin or irisin stimulated granulosa cell E2 production (1.4-fold, p<0.05 and 2.5-fold, p=0.0002, respectively), but when insulin and irisin were used in combination, this stimulatory effect on E2 production was abolished. We conclude that irisin may have reproductive axis effects in the pituitary and in the ovary. Further studies are needed to confirm these initial observations and to explore the mechanisms of irisin effects in the reproductive system.