**2. Leptin regulation of reproduction**

The overall importance of leptin to reproduction was established soon after its discovery [5]. Leptin alone will restore fertility in leptin-deficient animals and humans [4, 15, 16, 27–36]. There are distinct sex differences in serum leptin levels in the adult. After puberty, adult males have relatively low leptin levels, when compared with females [37–41]. This sex difference may reflect the differential regulation of leptin by gonadal steroids. Androgens inhibit leptin secretion to prevent leptin inhibition of testicular function (reviewed in [5]). In females by contrast, estrogens stimulate leptin secretion. The rise in estrogen early in the cycle may contribute to the 2-3-fold increase in leptin levels known as the midcycle leptin surge [37, 39].

With respect to gonadotrope function, studies have also reported a synchrony between nocturnal leptin and LH pulses in normal cycling women [36, 37]. Indeed, a comprehensive study of 259 cycling women reported that the highest levels of leptin were correlated with the timing of the LH surge [37]. In contrast, anovulatory cycles were associated with overall low leptin levels.
