ABSTRACT
It is now recognized that appropriate regulation of reproduction, energy intake, and
energy expenditure, and thus maintenance of body weight and fertility, relies on complex
hypothalamic neurocircuitry. Feeding and reproductive function are closely linked.
During times of undernourishment and falling body fat the reproductive axis is down-regulated.
Circulating factors and hypothalamic circuits coordinate these responses. Leptin has
been described to be an important peripheral signal that indicates body fat stores
to the hypothalamus and thus links nutrition and reproduction. Leptin acts by altering
neuropeptide circuits in the hypothalamus, which alter gonadotropin-releasing hormone
release and food intake. The importance of key neuropeptide systems identified in
rodents is now being established in man. Notably mutations in the melanocortin MC4
receptor are found in up to 4% of the morbidly obese, and in a proportion of patients
with anorexia nervosa mutations have been identified in the agouti-related peptide
gene (AgRP), which codes for an endogenous antagonist of this receptor. Intranasal
administration of a melanocortin fragment known to activate the MC4 receptor decreases
adiposity in humans. The melanocortin system has been shown to influence the reproductive
axis in rodents. However, the role of the melanocortin system in the control of reproduction
in humans remains to be established. Since the discovery of leptin, attention has
also been focused on peripheral signals that regulate reproduction, food intake, and
energy expenditure, either directly or via feedback on hypothalamic circuits. Notable
new discoveries in this area include the gastric hormone ghrelin. Circulating ghrelin
stimulates food intake in rodents and humans, although an influence on the reproductive
axis is yet to be reported.
KEYWORD
Hypothalamus - leptin - melanocortins - ghrelin - food intake
