Leptin and reproduction.

Since the cloning of leptin by Friedman's laboratory in 1994, over 3000 papers have been published on leptin, making it one of the most active research areas in all of science. Leptin appears to be a pleiotrophic hormone affecting many different tissues in the body. This review focuses on the role of leptin in reproduction. Evidence is accumulating that leptin potentially has roles in the regulation of GnRH and LH secretion, puberty, pregnancy, and lactation. Reciprocal regulation of leptin and its receptors by gonadal hormones and the implications and controversies thereof are also discussed in the review. Signaling pathways utilized by leptin are starting to become more clear, particularly JAK/STAT, MAPK, and SOCS3 have been implicated as mediators/modulators of leptin effects at the cellular level. At the hypothalamic level, there is also evidence that CART (cocaine and amphetamine-related transcript) is involved as a downstream mediator of leptin effects, especially with regards to control of GnRH secretion. While leptin clearly has many effects upon the reproductive axis, defining its precise roles is not without controversies. This review presents both pro and con findings, thereby demarking controversial areas that undoubtedly will be fertile ground for future investigation.