Leptin action in pubertal development: recent advances and unanswered questions

Abstract

In recent years we have witnessed a considerable advance in the understanding of the processes involved in pubertal development. This is partially due to the discovery of the kisspeptin system and its fundamental role in the control of reproductive physiology. In addition, the suspected relationship between increasing rates of childhood obesity and the apparent reduction in the age of puberty onset in girls has generated a growing interest in identifying the mechanisms by which nutrition may influence reproductive maturation. This review will focus on recent data unveiling the sites of leptin action in pubertal development that were generated using novel molecular techniques and genetically engineered mouse models. It will also emphasize areas of contention and the many relevant questions that remain unanswered.

Figure 1

Proposed neural pathway mediating leptin’s permissive effect on pubertal development. The ventral premammillary nucleus (PMV) expresses a dense collection of leptin receptor long-form (LepRb), sex steroids receptors (ER/estrogen receptor and AR/androgen receptor) and is responsive to environmental cues (odor and probably daylight, in seasonal breeders). Leptin stimulates PMV neurons which express glutamate and nitric oxide (NO). These PMV neurons innervate gonadotropin releasing hormone (GnRH) neurons and neurons in the anteroventral perivetricular nucleus (AVPV, supposedly those expressing Kiss1). This projection facilitates the increase in frequency of GnRH pulses and LH secretion at the onset of puberty.