Involvement of the somatostatin and cholinergic systems in the mechanism of growth hormone autofeedback regulation in the rat

Abstract

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)

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine

“…Thus, in humans atropine, a muscarinic cholinergic antagonist, or PZ, a more selective antagonist of muscarinic M1 receptors (Watson et al 1983), were able to suppress the GH release elicited by insulin hypoglycemia (Blackard & Waddel 1969), arginine (Casanueva et al 1984) or GHRH (Massara et al 1984), while conversely, pyridostigmine, an acetylcholinesterase (Ach-E) inhibitor, greatly enhanced the GH release elicited by GHRH , Ross et al 1987. Studies in both animals (Torsello et al 1988) and humans (Ross et al 1987) have also disclosed an important cholinergic link in the feedback action of GH, involving SS release.…”

“…Based on both animal (Casanueva et al 1983, Torsello et al 1988) and human studies , Ross et al 1987 it is now a tenet of the GH neuroendocrine control that muscarinic cholinergic agonists and antagonists act to inhibit or stimulate, respectively, hypothalamic somatostatinergic function and, in this way, modulate the action of CNS-or pituitaryacting GH secretagogues. Thus, in humans atropine, a muscarinic cholinergic antagonist, or PZ, a more selective antagonist of muscarinic M1 receptors (Watson et al 1983), were able to suppress the GH release elicited by insulin hypoglycemia (Blackard & Waddel 1969), arginine (Casanueva et al 1984) or GHRH (Massara et al 1984), while conversely, pyridostigmine, an acetylcholinesterase (Ach-E) inhibitor, greatly enhanced the GH release elicited by GHRH , Ross et al 1987.…”

Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs

“…In that respect, ARG has been shown to override inhibitory effects on GH secretion that are known to be mediated by an increase in somatostatin release, including glucose administration (Ghigo et al, 1992), obesity Martina et al, 1995), glucocorticoids (Giustina et al, 1992), advanced age (Ghigo et al, 1990b) and GH negative feedback (Massara et al, 1986;Torsello et al, 1988;Kelijman and Frohman, 1991;Ghigo et al, 1991). Cholinesterase inhibitors, such as neostigmine (NEO) and pyridostigmine, which are known to decrease somatostatin release (Richardson et al, 1980;Muller, 1987) do not further increase GH response to ARG in human (Massara et al, 1986;Ghigo et al, 1990aGhigo et al, , 1994Procopio et al, 1995).…”

Acute Hyperglycemia and Activation of the .BETA.-Adrenergic System do not Exhibit Synergistic Inhibitory Actions on Thyrotropin-releasing Hormone (TRH)-induced Thyroid Stimulating Hormone (TSH) Secretion

“…These findings exclude the possibility that glucose may act by inhibiting endogenous TRH release. However, activation of the cholinergic system inhibits the release of SRIH from the rat hypothalamus in vitro [3] and in vivo [4,17,25] and pyridostigmine increases TRH-induced TSH secretion in humans [26]. Therefore, it is believed that acute hyperglycemia suppresses TSH release from the anterior pituitary gland by cholinergic stimulation of hypothalamic SRIH release.…”