Noradrenergic modulation of human pancreatic growth hormone-releasing factor (hpGHRF1-44)-induced growth hormone release in conscious male rabbits: involvement of endogenous somatostatin.
To clarify the role of noradrenergic neurons in the regulation of GH secretion, the effects of iv administered noradrenergic antagonists were investigated in freely moving, conscious male rabbits. During a 6-h observation period (1030-1630 h), control rabbits manifested pulsatile GH secretion with surges between 1030-1200 and 1415-1630 h. Phenoxybenzamine, (POB), an alpha-adrenergic blocker (5 mg/kg, twice), abolished the episodic GH surges; propranolol, a beta-adrenergic blocker (2.5 mg/kg, twice), did not. The bolus injection (1 or 10 micrograms) of synthetic human pancreatic GH-releasing factor (hpGHRF) with 44 amino acid residues (hpGHRF1-44) resulted in significant rises in the plasma GH of control animals. The plasma GH responses to hpGHRF1-44 were significantly larger in propranolol-treated than control rabbits. In contrast, POB completely suppressed the hpGHRF1-44-induced GH release. The injection of antisomatostatin (SRIF) serum into POB-treated rabbits did not yield a disinhibition of the episodic GH surges but restored the plasma GH rises after hpGHRF1-44 injection. These results indicate that noradrenaline++ plays an important role in regulating GH secretion in the rabbit. We propose that alpha-noradrenergic blockade suppresses GH release not only by inhibiting the release of hypothalamic GHRF but also by stimulating the secretion of SRIF and that beta-noradrenergic blockade enhances GH release by inhibiting the release of SRIF from the hypothalamus.
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D003243:Consciousness / Q000502:physiology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010179:Pancreas / Q000502:physiology*; D010187:Pancreatic Hormones / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D013004:Somatostatin / Q000502:physiology*
D010187:Pancreatic Hormones; D010446:Peptide Fragments; D010643:Phenoxybenzamine; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011433:Propranolol