CLONIDINE POTENTIATES THE GROWTH-HORMONE RESPONSE TO A GROWTH-HORMONE RELEASING 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 (GH) 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 combination, were tested in 3-month-old male rats made GH-releasing hormone (GH-RH) deficient neonatally by administration of monosodium glutamate (MSG; 4 mg/g body weight s.c.). To prevent the presumable decrease in the pituitary GH content in these animals from leading to an erroneous interpretation of the results obtained, half of these rats were given GRF (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 received saline during these days (MSG-S and controls, respectively). To establish the efficiency of GRF priming, the pituitary GH content was measured in other MSG-GRF, MSG-S, and control animals. The mean (+/- SEM) GH peaks in response to GRF challenge were significantly higher in controls 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 different pituitary GH content, significantly (p < 0.01) higher in controls than 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 response to the alpha(2)-adrenergic agonist (25 +/- 3.2 mu g/l) in controls was significantly lower (p < 0.01) than that elicited by GRF. Pretreatment with CLO significantly (p < 0.01) enhanced the GH response to GRF in control (640.6 +/- 57.9 mu g/l) and in MSG-GRF rats (324.3 +/- 76.4 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 GH response to GRF in GH-RH-deficient rats. Since we have reported a similar synergistic effect in rats exhibiting pharmacologically increased SS release, it can be concluded that, in this species, CLO acts by inhibiting the hypothalamic release of SS rather than by stimulating endogenous GH-RH release.