Additionally, recent studies indicate that injections of leptin to ob/ ob mice, which have a congenital deficiency in leptin and are infertile, increase numbers of graafian follicles and correct their infertility . Although the positive effect of leptin on thecal cell proliferation observed in the present study is consistent with these previous observations, the inhibitory effect of leptin on thecal cell steroidogenesis is not.
It is unlikely that the leptin-induced decrease in steroid production in the present study was due to increased cell proliferation per se because 1) insulin also increased cell proliferation but increased steroid production, and 2) leptin’s stimulatory effect (i.e., 16% increase) on cell proliferation was much smaller than its inhibitory effect (i.e., > 80% inhibition) on steroid production. Furthermore, these in vitro effects of leptin observed in the present studies are not due to a change in cell viability since insulin, leptin, and their combined treatment had no effect on cell viability. A recent study has shown that recombinant mouse leptin can also inhibit insulin-like growth factor-I-induced estradiol production by cultured rat granulosa cells and insulin-induced estradiol production by cultured bovine granulosa cells . Thus, recent in vitro data indicate that leptin may exert a direct inhibitory effect on ovarian function in vivo. It is important to point out that, in vivo, leptin may have multiple sites of action within the hypothalamic-pituitary-ovarian axis and therefore positively or negatively impact other reproductive tissue. In support of this notion, serum LH and FSH concentrations were increased in ob/ob mice receiving injections of leptin , and glutamatergic excitatory postsynaptic current in the arcuate nucleus was reduced with leptin treatment.