Results of the present studies have indicated that 1) leptin inhibits insulin-induced progesterone and androstenedione production by thecal cells; 2) leptin increases insulin-induced thecal cell numbers without affecting thecal cell viability; 3) leptin does not compete for [125I]insulin binding; and 4) specific binding of 125I-leptin is demonstrable in cultured thecal cells. birth control pills
Similar to previous researchers , we found that insulin was a potent stimulator of thecal cell proliferation and steroidogenesis. However, results of the present study show for the first time that leptin may directly antagonize insulin’s stimulatory effect on thecal cell steroidogenesis. Because concentrations of leptin in blood of lean and obese women range from 2 to 10 ng/ml and 10 to 100 ng/ml, respectively, the present results indicate that leptin at concentrations found in human circulation may have a direct impact on ovarian thecal cell function. It is important to note that the sequence of the 145-amino acid form of secreted leptin is highly conserved across species. Specifically, bovine leptin (GenBank accession number P50595) has 85% homology with mouse and rat leptin and 86% homology with human leptin. Thus, the effects of mouse leptin and bovine leptin on bovine ovarian cell function would probably yield similar results, but this awaits verification. Although the locus of leptin’s action on thecal steroidogenesis will also require additional studies, results of the present study indicate that the inhibitory effect of leptin on insulin action is not mediated by direct inhibition of insulin binding to its receptor. The insulin binding assay used in the present study has been used previously and is not likely to be influenced in a major way by the low amount of insulin receptor internalization that probably occurs at 22°C . A recent report indicates that leptin can attenuate tyrosine phosphorylation of the insulin receptor substrate-1 in cultured HepG2 cells , but whether this is the mechanism operative in thecal cells remains to be determined.