In 1994, the gene for the protein leptin was cloned and sequenced from both the mouse and human. Leptin is a 167-amino acid protein made and secreted by adipocytes. The finding that leptin circulates in the plasma in proportion with body adiposity led to the theory that leptin acts as an ‘‘adipostat,’’ a humoral signal carrying information regarding energy reserves. Both peripheral and central injections of leptin to wild-type mice cause weight loss and reduced food intake. The possibility of a link between leptin and reproduction became apparent when it was determined that a homozygous mutation in the leptin (ob) gene was responsible for the obesity syndrome in the obese (ob/ob) mouse. Several papers testified to the reproductive shortcomings of ob/ob mice after the first published work on this mutant. buy birth control online
These mice are infertile, a condition believed to be due to reduced circulating gonadal steroids and insufficient hypothalamic-pituitary drive. Experiments from this laboratory and others have demonstrated that correction of leptin deficiency in ob/ob mice by peripheral injections of recombinant leptin activates the reproductive axis and restores fertility in both sexes.