CLONIDINE POTENTIATES THE GROWTH-HORMONE RESPONSE TO A GROWTH-HORMONERELEASING HORMONE CHALLENGE IN HYPOTHALAMIC GROWTH-HORMONE RELEASING HORMONE-DEFICIENT RATS

This study was designed to further investigate our postulate regarding the inhibitory role played by central alpha(2)-adrenergic pathways on hypothalamic somatostatin (SS) release in rats. The growth hormone (G H) responses to exogenous GH-releasing factor (GRF; 3 mu g/kg i.v.) or clonidine (CLO; 100 mu g/kg i.v.), either given alone or in combinati on, were tested in 3-month-old male rats made GH-releasing hormone (GH -RH) deficient neonatally by administration of monosodium glutamate (M SG; 4 mg/g body weight s.c.). To prevent the presumable decrease in th e pituitary GH content in these animals from leading to an erroneous i nterpretation of the results obtained, half of these rats were given G RF (MSG-GRF rats; 30 mu g/kg s.c.) for 3 days immediately prior to GH testing. The other half of MSG-treated and non MSG-treated rats receiv ed saline during these days (MSG-S and controls, respectively). To est ablish the efficiency of GRF priming, the pituitary GH content was mea sured in other MSG-GRF, MSG-S, and control animals. The mean (+/- SEM) GH peaks in response to GRF challenge were significantly higher in co ntrols than in MSG-GRF rats (125.2 +/- 28.5 vs. 67.5 +/- 19.4 mu g/l; p < 0.05), while no significant GRF-induced GH release was observed in the MSG-S group. Most likely these results are related to the differe nt pituitary GH content, significantly (p < 0.01) higher in controls t han in MSG-GRF rats, and in the latter higher than in MSG-S animals (p < 0.05). CLO administration did not evoke a significant GH release in MSG rats, whether primed with GRF or not. The maximal GH peak in resp onse to the alpha(2)-adrenergic agonist (25 +/- 3.2 mu g/l) in control s was significantly lower (p < 0.01) than that elicited by GRF. Pretre atment with CLO significantly (p < 0.01) enhanced the GH response to G RF in control (640.6 +/- 57.9 mu g/l) and in MSG-GRF rats (324.3 +/- 7 6.4 mu g/l), but it produced no effect in MSG-S animals. These results indicate that alpha(2)-adrenergic agonism is able to potentiate the G H response to GRF in GH-RH-deficient rats. Since we have reported a si milar synergistic effect in rats exhibiting pharmacologically increase d SS release, it can be concluded that, in this species, CLO acts by i nhibiting the hypothalamic release of SS rather than by stimulating en dogenous GH-RH release.