METABOLIC CONTROL OF SEXUAL FUNCTION AND GROWTH - ROLE OF NEUROPEPTIDE-Y AND LEPTIN

The discovery of leptin has generated an extraordinary interest in the field of obesity but also in the understanding of the relationship be tween metabolic status and the neuroendocrine system. Following the in itial demonstration that leptin administration to fasting mice can 'pr otect' neuroendocrine secretions and prevent the changes that are asso ciated with fasting, the concept has emerged that a normal leptin secr etion is a prerequisite for normal neuroendocrine secretions. Several unfavorable metabolic situations are associated with low plasma leptin , increased secretion of hypothalmic neuropeptide Y (NPY), and hypogon adism, and a causal relationship has been evoked. Severe dietary restr iction in juvenile female rats is associated with low plasma leptin an d sexual immaturity. Cessation of food restriction leads to immediate increase in plasma leptin followed 4 days later by vaginal opening. If food restriction is maintained, central leptin infusion can induce se xual maturation, thus demonstrating that leptin can act as a signal fo r the onset of puberty. In untreated type-I diabetic rats, hypogonadis m is associated with very low plasma leptin and increased hypothalmic NYP synthesis and oestrous cyclicity. Fasting rapidly inhibits growth hormone (GH) secretion in association with low plasma leptin and eleva ted hypothalmic NPY. Central infusion of leptin to fasting rats was ab le to completely prevent the collapse of GH secretion and to maintain a normal low NPY synthesis. In summary, normally elevated plasma level s appear to be a prerequisite for normal GH and gonadotropin secretion in the rat. Degradation of metabolic conditions results in a rapid re duction of circulating leptin that could represent the signal for seve ral alterations of neuroendocrine secretions. At the level of the hypo thalamus, leptin could act on NPY neurons to transduce part or all of this 'metabolic' message, The possibility that changing plasma levels for leptin also affect peripheral endocrine targets, such as pituitary , ovary, adrenal or pancreas, is likely since these endocrine organs e xpress functional long-term leptin receptors. (C) 1998 Elsevier Scienc e Ireland Ltd. All rights reserved.