Leptin signaling and circuits in puberty and fertility

Carol F Elias,Darshana Purohit

doi:10.1007/s00018-012-1095-1

Abstract

Leptin is an adipocyte-derived hormone involved in a myriad of physiological process, including the control of energy balance and several neuroendocrine axes. Leptin-deficient mice and humans are obese, diabetic, and display a series of neuroendocrine and autonomic abnormalities. These individuals are infertile due to a lack of appropriate pubertal development and inadequate synthesis and secretion of gonadotropins and gonadal steroids. Leptin receptors are expressed in many organs and tissues, including those related to the control of reproductive physiology (e.g., the hypothalamus, pituitary gland, and gonads). In the last decade, it has become clear that leptin receptors located in the brain are major players in most leptin actions, including reproduction. Moreover, the recent development of molecular techniques for brain mapping and the use of genetically modified mouse models have generated crucial new findings for understanding leptin physiology and the metabolic influences on reproductive health. In the present review, we will highlight the new advances in the field, discuss the apparent contradictions, and underline the relevance of this complex physiological system to human health. We will focus our review on the hypothalamic circuitry and potential signaling pathways relevant to leptin’s effects in reproductive control, which have been identified with the use of cutting-edge technologies of molecular mapping and conditional knockouts.

Highlights

Leptin is a hormone primarily synthesized and secreted by the white adipose tissue [362]
Leptin receptors are expressed in many organs and tissues, including those related to the control of reproductive physiology
As in db/db and ob/ob mice, the expression of hypothalamic POMC mRNA was reduced and AgRP mRNA was increased compared with control mice, demonstrating that STAT3 is required for the regulation of both mRNAs [23]; but while db/db and ob/ob mice were infertile, s/s mice showed improved fertility indicating that normalization of melanocortin levels in the brain is not required for improvement of the reproductive function

Summary

Introduction

Leptin is a hormone primarily synthesized and secreted by the white adipose tissue [362]. The selective deletion of leptin-induced STAT3 signaling in cells that express LepR (LRbS1138 s/s mice) recapitulates most of the db/db metabolic phenotype, producing hyperphagia, high adiposity and disruption of the melanocortin circuitry in both males and females [23].

Results

Conclusion