Leptin, the recently identified adipose obese (ob) gene product, is a plasma protein hormone that parallels the amount of fat reserves and is thought to regulate satiety. The initial 167-amino acid sequence of leptin is highly conserved (i.e., 83-97% homology) as is the 145-amino acid sequence (the secreted form) of leptin (84-97% homology) across the four species (mouse, rat, human, monkey) in which it has been characterized. If genetically obese (ob/ob) mice that lack endogenous leptin receive injections of leptin, they experience decreased food intake, a loss in body weight, increased ovarian weight and number of follicles, and correction of a sterility defect. The latter observations indicate that leptin may have positive influences on the reproductive system. However, the majority of women with polycystic ovary disease are obese, insulin-resistant, and anovulatory, suggesting that leptin may also have negative impacts on the reproductive system. Whether systemic leptin concentrations correlate with body fat in cattle remains to be determined.
Recent evidence shows that patients with noninsulin-dependent diabetes mellitus (NIDDM) have significantly greater concentrations of leptin in their circulation than do their respective control groups. Furthermore, NIDDM patients are insulin-resistant, suggesting that leptin may influence a tissue’s response to insulin. Indeed, a recent study has shown that leptin can attenuate tyrosine phosphorylation of the insulin receptor substrate-1 in cultured HepG2 cells. Similar to obese humans, obese heifers are insensitive to the glucoregulatory effects of exogenous insulin, but whether this is due to differences in the amount of leptin remains to be determined. buy diabetes drugs
Insulin has long been known to have direct effects on ovarian cell function in several species including humans, rats, and cattle and is thought to be involved in the clinical manifestation of increased androgenicity in patients with polycystic ovary disease, presumably via increased thecal androgen production. In humans, obesity also has been linked to obstetric complications. Similarly, obese heifers previously raised on a high plane of nutrition have increased calving difficulty compared with lean heifers previously raised on a low plane of nutrition. However, in mature cows, reproductive performance decreases as body fat content decreases. Therefore, we hypothesized that leptin may directly influence insulin-stimulated ovarian follicular function, and we set out to determine the effect of leptin on insulin-induced proliferation and steroidogenesis of bovine thecal cells in vitro.