HYPOTHALAMIC MEDIATED ACTION OF FREE FATTY-ACID ON GROWTH-HORMONE SECRETION IN SHEEP

Experimental data suggest that elevated FFA levels play a leading role in the impaired GH secretion in obesity and may therefore contribute to the maintenance of overweight. GH has a direct lipolytic effect on adipose tissue; in turn, FFA elevation markedly reduces GH secretion. This suggests the existence of a classical endocrine feedback loop bet ween FFA and GH secretion. However, the FFA mechanism of action is not yet understood. The involvement of somatostatin (SRIH) is controversi al, and in vitro experiments suggest a direct effect of FFA on the pit uitary. In sheep it is possible to collect hypophysial portal blood an d quantify SRIH secretion in hypophysial portal blood under physiologi cal conscious and unstressed conditions. In this study we determined t he effects of FFA (Intralipid and heparin) infusion on peripheral GH a nd portal SRIH levels in intact rams chronically implanted with perihy pophysial cannula and in rams actively immunized against SRIH to furth er determine SRIH-mediated FFA effects on GH axis. Immediately after i nitiation of Intralipid infusion, we observed a marked increase in the FFA concentration (2160 +/- 200 us. 295 +/- 28 nmol/ml; P < 0.01) as well as a significant decrease in basal GH secretion (1.8 +/- 0.1 us. 2.5 +/- 0.3 ng/ml; P < 0.05) and a drastic reduction of the GH respons e to iv GH-releasing hormone injection (4.8 +/- 0.7 ng/ml in FFA group us. 35.8 +/- 9.7 ng/ml in saline group; P < 0.01). No change in plasm a insulin-like growth factor I levels was observed. During the first 2 h of infusion, the GH decrease observed was concomitant with a signif icant increase in portal SRIH levels (22.1 +/- 3.2 vs. 13 +/- 1.6 pg/m l; P < 0.01). In rams actively immunized against SRIH, the effect of F FA on basal GH secretion was biphasic. During the first 90 min of infu sion, the decrease in GH induced by FFA was significantly blunted in r ams actively immunized against SRIH (57 +/- 9% for immunized rams vs. 23.5 +/- 2.5% for control rams). This corresponds to the period of inc reased SRIH portal levels. After this first 90-min period, no differen ce was seen between control and immunized rams. Our results show that FFA exert their inhibitory action on the GH axis at both pituitary and hypothalamic levels, the latter mainly during the first 90 min, throu gh increased SRIH secretion.