Aim: 

Present study was designed to test the influence of estradiol and/or progesterone replacement therapy to ovariectomized rats on insulin signalling.

Methods: 

Four experimental groups of virgin female Wistar rats were designed: ovariectomized treated during 6, 11 and 16 days with progesterone, estradiol, estradiol/progesterone and placebo. The day of killing, rats were anesthetized and clamp experiment was performed. 17ß-estradiol and progesterone were determined by RIA. Adipose tissue was recovered and processed. Glut4 amount and IRS-1 serine 612 and tyrosine phosphorylation was detected by Western Blot. IRS-1 was inmunoprecipitated and p85 alpha interaction was detected. Analysis of Variance and Student-Newman-Keuls were employed. A p<=0.05 was considered significant. Animal procedures were according with current and National Guidelines.

Results and Conclusion: 

Present results show that progesterone treatment to ovariectomized rats promotes a significant increase on body weight which is reverted by estradiol treatment. Moreover, progesterone treatment regulates insulin sensitivity on a dose-dependent way, higher plasma levels of progesterone decrease insulin sensitivity while lower levels increase the sensitivity. 17b-estradiol/progesterone combination modulates this effect, higher levels decrease insulin sensitivity and lower levels increase insulin sensitivity. The analysis of key proteins involved on insulin signalling showed that higher plasma levels of progesterone are able to decrease IRS-1 tyrosine phosphorylation while lower levels increase IRS-1 serine 612 phosphoryation. The combination of estradiol/progesterone modulates progesterone actions on a dose-dependent way. We can conclude that the balance between IRS-1 serine 612 and tyrosine phosphorylation is very important in order to understand the effects of ovarian steroids on insulin sensitivity.