Leptin is a metabolic signal to the reproductive system.

Abstract

Leptin, a newly-discovered hormonal product of the obese (ob) gene, is expressed by adipocytes and thought to play a role in the regulation of food intake and metabolism. We tested the hypothesis that leptin signals metabolic information to the reproductive system by examining its effects on the reproductive system of ob/ob mice, which have a congenital deficiency in leptin and are infertile. We treated pair-fed males and females with leptin (50 microg twice daily, ip) or vehicle (n=10/group) for 14 days, after which the animals were bled and killed. Leptin-treated females had significantly elevated serum levels of LH, increased ovarian and uterine weights, and stimulated aspects of ovarian and uterine histology compared to controls. Leptin-treated males had significantly elevated serum levels of FSH, increased testicular and seminal vesicle weights, greater seminal vesicle epithelial cell height, and elevated sperm counts compared to controls. These results demonstrate that leptin stimulates the reproductive endocrine system in both sexes of ob/ob mice and suggest that leptin may serve as a permissive signal to the reproductive system of normal animals.

Effect of Central Antileptin Antibody on the Onset of Female Rat Puberty

“…One indication that leptin is involved in centrally regulated maturation of the reproductive system was the discovery that ob/ob females are always sterile [6], and weight loss induced by dietary restriction fails to correct their sterility. Importantly, their fertility can be reversed by leptin treatment in both sexes [7, 8]. The ob/ob leptin deficient and db/db leptin resistant mouse models have greatly advance our understanding regarding the pivotal role of leptin in reproduction [9, 10].…”

Effects of Recombinant Human Leptin (Metreleptin) on Nocturnal Luteinizing Hormone Secretion in Lipodystrophy Patients

“…In vitro, leptin acutely stimulates basal and GnRH-induced LH release from the pituitary. Consistent with this, leptin administration to leptin-deficient ob/ob mice reverses hypogonadotropic hypogonadism and anovulation [13]. …”

Leptin and the treatment of obesity

“…Female ob/ob mice are sterile and are constantly in a prepubertal stage of development. Ovarian weights, sex steroid concentrations, and pituitary gonadotropin concentrations have been found to be low in these animals [Barash et al, 1996], while administration of recombinant leptin to female ob/ob mice completely restored gonadotropin secretion, secondary sex organ weight and function, and fertility [Barash et al, 1996;Chehab et al, 1996]. Male ob/ob mice demonstrate similar low levels of fertility, with low gonadotropin secretion and hypogonadism reported [Swerdloff et al, 1978;Mounzih et al, 1997].…”