LEPTIN ALTERS THE RESPONSE OF THE GROWTH-HORMONE RELEASING-FACTOR GROWTH-HORMONE INSULIN-LIKE GROWTH-FACTOR-I AXIS TO FASTING

Proper nutritional status is critical for maintaining growth and metab olic function, playing an intimate role in neuroendocrine regulation. Leptin, the recently identified product of the obese gene, may very we ll be an integral signal which regulates neuroendocrine responses in t imes of food deprivation, The present study examines leptin's ability to regulate hormonal synthesis and secretion within the GRF-GH-IGF axi s in the adult male rat during almost 3 days of fasting. Serum levels of GH and IGF-I were drastically suppressed by fasting, Daily leptin a dministration was able to fully prevent the fasting-induced fall in se rum GH, Leptin failed to restore IGF-I to control levels, however, sug gesting possible GH resistance. Fasting caused an insignificant increa se in GH mRNA, while leptin injections significantly increased steady- state levels of this message. The GRF receptor (GRFr) message was not altered with fasting or leptin treatment. Leptin also exhibited effect s at the hypothalamic level. Fasting induced a sharp fall in GRF mRNA expression and leptin injections partially prevented this fall, Howeve r, there were no observed changes in the hypothalamic GRF content. The se results provide evidence that leptin may function as a neuromodulat or of the GRF-GH-IGF axis communicating to this hormonal system the nu tritional status of the animal.