Effects of cysteamine on pulsatile growth hormone release and plasma insulin concentrations in sheep

The effects of cysteamine (CSH; 0, 50, or 100 mg/kg BW), a somatostatin depleting agent, on growth hormone (GH) and insulin (INS) secretion were studied in sheep (Ovis aries). Cysteamine was administered as a single intragastric bolus on day 0 (0900). Jugular blood samples were collected at 15-min (GH) and 2-hr (INS) intervals over an 8-hr period (1100-1900) on day 0, 3, and 7. Intragastric administration of CSH at 50 mg/kg BW augmented (quadratic, P = .04) mean plasma GH concentration, with the greatest response occurring on day 3. Baseline GH concentrations were elevated in wethers dosed with 50 mg/kg BW CSH on day 3, whereas wethers dosed with 100 mg/kg BW CSH had lower baseline GH concentrations on day 0 (CSH x day interaction, P = .02). Cysteamine administration increased GH pulse amplitude (quadratic, P = .15), with the greatest magnitude of change occurring with 50 mg/kg BW CSH on day 0 and 3. Frequency of GH pulses was increased (quadratic, P = .10) following CSH treatment. Administration of 100 mg/kg BW CSH augmented plasma INS on day 0 (CSH × day interaction, P = .09). These findings indicate that CSH alters GH and INS secretion in a dose-dependent and temporal manner. The observed changes in mean and baseline plasma GH concentrations associated with 50 mg/kg BW CSH are consistent with somatostatin depletion; however, higher doses of CSH appear to disrupt GH secretion by an alternative mechanism.