STUDIES OF GROWTH-HORMONE SECRETION IN CALORICALLY RESTRICTED DOGS - EFFECT OF CHOLINERGIC AGONISTS AND ANTAGONISTS, GLUCOSE AND THYROTROPIN-RELEASING-HORMONE

The effect of caloric restriction (CR) on the growth hormone (GH) response to compounds reportedly capable of acting via somatostatinergic influences, i.e. cholinergic agonist or antagonist drug, glucose or thyrotropin-releasing hormone (TRH), administered alone or combined with GH-releasing hormone (GHRH), was evaluated in dogs. Eight beagle dogs, aged 4-5 years, underwent a 26-day period of increasing CR; they were evaluated either under basal conditions or starting from day 13 of CR, according to a schedule which allowed the mean length of CR to be similar among individual tests. CR resulted in a significant increase in basal GH levels, and starting from day 13 in a significant decrease in plasma somatomedin C levels; plasma glucose levels were significantly diminished on day 13 of CR and then remained unaltered. Administration of GHRH (GHRH1-44, 2-mu-g/kg, i.v.) induced a rise in plasma GH levels strikingly higher during CR than under basal conditions. Pyridostigmine (2 mg/kg orally), a muscarinic cholinergic agonist reportedly capable of restraining hypothalamic release of somatostatin (SS), enhanced the GH response to GHRH under basal conditions, but failed to do so during CR. Conversely, pirenzepine (0.6 mg/kg, i.v.), a muscarinic cholinergic antagonist, abolished the GHRH-induced GH rise under basal conditions, but only reduced it during CR. Only by doubling the dose of pirenzepine was complete inhibition of the GHRH-induced GH rise effected. Glucose alone (2 g/kg, p.o.) failed to modify basal GH secretion either before or during CR, but significantly inhibited the GHRH-induced GH rise either before or during CR. TRH (5-mu-g/kg, i.v.) did not modify plasma GH levels under basal conditions, but partially counteracted the rise in plasma GH occurring during CR. Like glucose, TRH significantly inhibited the GHRH-induced GH rise either before or during CR. Neither glucose nor TRH alone induced a 'paradoxical' rise in plasma GH during CR. In summary, (1) the data obtained with drugs affecting cholinergic transmission suggest that the latter is increased in dogs during CR and this likely results in a reduced hypothalamic SS tone, and (2) the data obtained with glucose and TRH suggest that these compounds may be effective to trigger not only hypothalamic SS release but also synthesis or, alternatively, they may act via inhibitory influences other than SS.