The involvement of the cholinergic system in GH secretion has recently acquired increasing importance. Data have been presented suggesting that in rats the effect of cholinergic modulation on GH secretion takes place through inhibition or stimulation of hypothalamic somatostatin (SRIF) release. To investigate further the significance of cholinergic-SRIF link and its role in the regulation of GH secretion, the action of cholinergic agonist and antagonist drugs in the GH short-loop feedback mechanism mediated by SRIF was investigated. Intracerebroventricular (i.c.v.) infusion of 0.2 or 2.0 micrograms GH/rat into the lateral brain ventricle of adult male rats induced a significant reduction in the GH-releasing hormone (GHRH; 2 micrograms/kg, i.v.)-induced peak GH rise, but only the 2.0 micrograms dose reduced also the GH-integrated area after administration of GHRH. This effect was absent after central administration of 20.0 micrograms GH/rat, due probably to leakage of some GH from the cerebral ventricle into the systemic circulation. Pretreatment with cysteamine (300 mg/kg, s.c.), a known depletor of hypothalamic SRIF, or with anti-SRIF serum (0.5 ml/rat) completely counteracted the lessening of the GH response to GHRH induced by 2.0 micrograms GH injected i.c.v. Similarly, pretreatment with the cholinergic agonist pilocarpine (3 mg/kg, i.v.) completely antagonized the inhibitory effect of central infusion of GH on the GHRH-induced GH response. Atropine (1.0 mg/kg, i.v.), a muscarinic cholinergic antagonist, strikingly inhibited the GHRH-induced GH rise, but when given in combination with i.c.v. infusion of GH there was no additive inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The involvement of the cholinergic system in growth hormone (GH) secretion has acquired increased importance in the last few years. In rats, pretreatment with muscarinic cholinergic agonists potentiates the GH release induced by GH-releasing hormone (GHRH), via inhibition of somatostatin (SRIF) release from the hypothalamus. The aim of this study was to validate the use of cholinergic agonists to probe the functional activity of the hypothalamic SRIF system. It is known that hypothalamic SRIF displays an age-related increase in its functional activity; therefore, rats from 10 days to 29 months of age were used and challenged with GHRH following acute administration of pilocarpine, a cholinergic muscarinic agonist. Following administration of GHRH alone there was an age-related decline in GH responsiveness. Administration of pilocarpine potentiated the GH response to GHRH during the entire life-span of the rats, the only exception being 10-day-old rats in which the drug was without effect. Pilocarpine, though effective in potentiating the GH response to GHRH, did not restore, in senescent rats, GH stimulation to the level of that present in young (3-month old) or adult rats (8-month old). However, the drug was effective in rejuvenating the GH response to GHRH of the older rats (29- and 18-month old) to the level of 15-month-old rats. The present results indicate that modulation of the GH response to GHRH by pilocarpine is consonant with the known changes in the activity of hypothalamic SRIF. Cholinergic drugs may therefore represent a valuable tool to assess SRIF function in physiologic or pathologic conditions of GH secretion, and, in addition, to potentiate GH release during a course of GHRH therapy.

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