Cysteamine effects on growth hormone secretion in the male rat.

Abstract

The thiol agent cysteamine (CSH) is reported to deplete immunoreactive somatostatin (SS) in the central nervous system and the gastrointestinal tract of rats. We investigated whether CSH, given sc, alters physiological GH secretion in chronically cannulated male rats. A dose of 300 mg/kg totally disrupted episodic GH secretion, causing an elevation of GH baseline levels and an absence of GH secretory bursts. CSH at a dose of 90 m/gg elevated GH trough levels and slightly reduced GH peak amplitudes, whereas a dose of 30 mg/kg did not affect episodic GH secretion. GH patterns remained disrupted in most animals on day 2 after drug administration, but returned to normal by 1 week. The administration of anti-SS serum resulted in a further elevation of GH levels in CSH-treated animals. Both clonidine and morphine induced a GH rise in treated animals. The GH response to stress was attenuated in CSH-treated animals. CSH at the highest dose given (300 mg/kg) markedly reduced norepinephrine (NE) concentrations (56% of the control value) in the hypothalamus and median eminence 4 h after administration. In the same animals, dopamine was elevated (200%) in the hypothalamus, but was unaffected in the median eminence. The changes in catecholamine levels are consistent with the hypothesis that CSH inhibits the enzyme dopamine-β-hydroxylase. Furthermore, blockade of NE synthesis with the dopamine-β-hydroxylase inhibitors diethyldithiocarbamate (500 mg/kg) or fusaric acid (100 mg/kg) completely suppressed episodic GH secretion. These findings indicate that CSH has an important effect on physiological GH secretion and that its effect is dose dependent and reversible. Lower doses appear to have a specific effect on SS-mediated inhibition of GH secretion. On the other hand, high doses of CSH totally disrupt GH secretion by affecting both the SS inhibitory and the GRF stimulatory components of episodic GH secretion. The latter action of CSH is, perhaps, mediated by both an inhibition of the synthesis of NE in the hypothalamus and an acute stress response.