Clonidine Potentiates the Growth Hormone (GH) Response to GH-Releasing Hormone in Norepinephrine Synthesis-Inhibited Rats: Evidence for an Alpha-2-Adrenergic Control of Hypothalamic Release of Somatostatin

Abstract

The aim of this study was to investigate whether central α₂-adrenergic pathways act, in rats, by inhibiting somatostatin (SS) release, as it has been postulated to occur in other species. The growth hormone (GH) responses to GH-releasing hormone (GRF, 3 µg/kg i.v.) or clonidine (CLO, 100 µg/kg, i.v.), either given alone or in combination, were tested in male rats in which norepinephrine synthesis had been previously blocked with the dopamine-β-hydroxylase inhibitor diethyldithiocarbamate (DDTC, 400 mg/kg i.p.). These experiments were also carried out in a control group of animals that had been given placebo (P) instead of DDTC. The GH responses to GRF in the presence of anti-SS serum given to other P and DDTC rats, allowed us to assess whether DDTC treatment had induced increased SS secretion. GH tests were carried out during spontaneous (P) or pharmacologically induced (DDTC) trough periods. Therefore, the mean ( ± SEM) GRF-induced GH peak was similarly low in both groups of rats (P: 66.5 ± 16.6 µg/1; DDTC: 58 ± 14 µg/1). The administration of anti-SS serum significantly (p < 0.01) increased 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 administration 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 Prats (320 ± 50). Moreover, the former response was also significantly higher (p < 0.05) than that in P rats given anti-SS serum, although lower (p < 0.05) than that in DDTC animals which received this serum. In summary, α₂-adrenergic agonism was able to potentiate the GH response to GRF in the presence of either a physiologically or pharmacologically increased somatostatinergic tone. The existence of such a synergism between CLO and GRF indicates that they elicit GH release through different mechanisms. Since the GH responses to CLO + GRF were similar to those induced by GRF in P or DDTC rats given anti-SS serum, it is likely that in rats, as in other species, α₂-adrenergic pathways act in GH control by inhibiting the hypothalamic release of SS.

Effects of Atipamezole, an .ALPHA.2-Adrenergic Antagonist, and Somatostatin on Xylazine-lnduced Growth Hormone Release in Calves.

“…On the other hand, there are some reports which proposed that the stimulatory effect of clonidine, an a2-adrenoceptor agonist, on GH release is mainly exerted by inhibiting the hypothalamic SRIF release in rats [20][21][22] and man [23]. But the study by Magnan et al in sheep [24] has demonstrated that clonidine acts centrally to stimulate GH and that this effect is mediated through changes in GHRH release into hypophysial portal blood.…”

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite

“…Plasma GH levels and pituitary GH content were determined by RIA as previously described (Lima et al, 1993). Pituitary homogenates were diluted 1:5000 for determination.…”

“…Bloch et al (1984) showed that MSG treatment results in the complete loss of growth hormone releasing factor (GRF)-immunoreactive cell bodies within this nucleus and provokes a selective disappearance of GRF-immunoreactive fibres in the median eminence of rats. This technique has routinely been practised to produce functionally hypopituitary animals (Lima et al, 1993) for studies of short-term growth (Hermanussen et al, 1996).…”

Salivary gland is capable of GH synthesis under GHRH stimulation

“…For the GH determinations, the reagents provided by the NIADDK (Baltimore, MD, USA) were used as previously described (Lima et al 1993). The iodination of rat GH I-6 was performed using lactoperoxidase (Thorell & Johansson 1971).…”