Effect of ovarian hormones on glucose metabolism in mouse soleus muscle

The effects of ovarian steroid hormones on insulin binding and insulin-stimulated glucose metabolism were studied in soleus muscles isolated from groups of ovariectomized adult female mice treated orally for 10 weeks with replacement doses of 17 beta-estradiol (E2) (5 micrograms/kg X day) and progesterone (P) (1 mg/kg X day) alone and in combination. Groups of intact and ovariectomized mice were also treated with placebo. Total muscle insulin binding at 0.17 nM insulin was reduced by 32% in ovariectomized mice, and this effect was partially reversed by each of the sex steroid treatments. Ovariectomy was associated with a decrease (29%) in insulin-stimulated 2-deoxyglucose uptake, while E2 alone produced a 2-fold increase in insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and glycogenesis. P alone did not significantly alter these parameters of glucose metabolism, but P antagonized the effects of E2 when the two hormones were administered in combination. The results provide evidence that E2 promotes insulin-mediated glucose uptake and utilization in skeletal muscle. The data also indicate that E2 and P exert different effects at postreceptor sites of the insulin effector pathway.