Leptin would appear to play a role in relaying metabolic information to the reproductive axis, but the mechanism(s) by which this is accomplished remains unknown. The search for sites of leptin’s action began with the cloning of its receptor (Ob-R) in mice and humans. The Ob-R is a single-pass membrane receptor of the class I cytokine receptor family (reviewed in ). Multiple splice variants have been found, which have identical extracellular domains and either a long (~300 amino acids) or short (~30 amino acids) intracellular domain. Stimulation of the long form activates signal transducer and activator of transcription (STAT) proteins both in vivo and in vitro, whereas the short form is apparently incapable of signaling via this pathway. birth control yasmin
Classical parabiosis experiments (reviewed in ) predicted that other spontaneously obese animals, such as the diabetic mouse (db/db; ) and fatty rat (fa/fa; ), would be unable to respond to a circulating satiety factor (now known to be leptin). This prediction was verified when it was discovered that db/db mice and fa/fa rats, which are also infertile, both have mutations in the long form of the Ob-R that render it ineffective. A mutation causing premature truncation of the Ob-R in humans has also been linked to obesity and hypogonadism.