Metabolic regulation of the neuroendocrine axis in pigs.

Transition from the fed to fasted state occurs more rapidly in prepubertal pigs than in mature pigs. Insulin-like growth factor I (IGF-I), leptin and specific metabolites, such as glucose and free fatty acids (FFA), play a role in signalling metabolic status to the brain-pituitary axis. High serum concentrations of FFA or glucose suppressed the growth hormone (GH) response to GH releasing hormone (GHRH), whereas glucose inhibited and FFA enhanced pituitary LH response to GnRH. The site of action of FFA and glucose on LH and GH secretion is at the pituitary cell. In cultured pig pituitary cells, IGF-I suppressed the GH response to GHRH and enhanced basal LH secretion. However, intracerebroventricular injection of IGF-I failed to affect LH or GH secretion in prepubertal gilts. Acute fasting suppressed leptin secretion without affecting LH or GH secretion. Metabolic fuel restriction by decreasing glucose availability increased GH secretion, but decreased LH secretion in prepubertal gilts. However, serum leptin concentrations were unchanged. Thus, the effects of acute energy deprivation on LH and GH secretion are independent of changes in leptin secretion. Serum leptin concentrations, hypothalamic leptin receptor mRNA and oestrogen-induced leptin gene expression in fat increased with age and adiposity in pigs. This increase occurred at the time of expected puberty in intact pigs. An intracerebroventricular injection of leptin suppressed feed intake, but stimulated GH secretion in prepubertal gilts. Leptin stimulated GnRH release from hypothalamic tissue in vitro. These results identify putative signals that link metabolic status and neuroendocrine control of appetite, growth and reproduction and have implications for nutrition-related human health problems due to high fat diets.