CLONIDINE POTENTIATES THE GROWTH-HORMONE (GH) RESPONSE TO GH-RELEASING HORMONE IN NOREPINEPHRINE SYNTHESIS-INHIBITED RATS - EVIDENCE FOR ANALPHA-2-ADRENERGIC CONTROL OF HYPOTHALAMIC RELEASE OF SOMATOSTATIN

The aim of this study was to investigate whether central alpha2-adrene rgic pathways act, in rats, by inhibiting somatostatin (SS) release, a s it has been postulated to occur in other species. The growth hormone (GH) responses to GH-releasing hormone (GRF, 3 mug/kg i.v.) or clonid ine (CLO, 100 mug/kg, i.v.), either given alone or in combination, wer e tested in male rats in which norepinephrine synthesis had been previ ously blocked with the dopamine-beta-hydroxylase inhibitor diethyldith io-carbamate (DDTC, 400 mg/kg i.p.). These experiments were also carri ed out in a control group of animals that had been given placebo (P) i nstead of DDTC. The GH responses to GRF in the presence of anti-SS ser um given to other P and DDTC rats, allowed us to assess whether DDTC t reatment had induced increased SS secretion. GH tests were carried out during spontaneous (P) or pharmacologically induced (DDTC) trough per iods. Therefore, the mean (+/- SEM) GRF-induced GH peak was similarly low in both groups of rats (P: 66.5 +/- 16.6 mug/l; DDTC: 58 +/- 14 mu g/l). The administration of anti-SS serum significantly (p < 0.01) inc reased these responses (P: 413 +/- 22; DDTC: 695 +/- 36; p < 0.01 vs. P). CLO administration elicited a maximal GH peak significantly higher (p < 0.05) in P (20.5 +/- 3) than in DDTC rats (4.1 +/- 2); however, the former was significantly lower than GH responses to GRF. The admin istration of CLO significantly potentiated (p < 0.01) the GRF-induced GH response; this was significantly higher (p < 0.01) in DDTC (575 +/- 90) than in P rats (320 +/- 50). Moreover, the former response was al so significantly higher (p < 0.05) than that in P rats given anti-SS s erum, although lower (p < 0.05) than that in DDTC animals which receiv ed this serum. In summary, alpha2-adrenergic agonism was able to poten tiate the GH response to GRF in the presence of either a physiological ly or pharmacologically increased somatostatinergic tone. The existenc e of such a synergism between CLO and GRF indicates that they elicit G H release through different mechanisms. Since the GH responses to CLO + GRF were similar to those induced by GRF in P or DDTC rats given ant i-SS serum, it is likely that in rats, as in other species, alpha2-adr energic pathways act in GH control by inhibiting the hypothalamic rele ase of SS.