Neuroendocrine regulation of growth hormone secretion in sheep. IV. Central and peripheral cholecystokinin

The result of alterations in the levels of CCK, in the blood and in the cerebrospinal fluid, on the functioning of the growth hormone axis has been examined in sheep. Male Coopworth sheep of about 40 kg liveweight were given various doses of CCK either intracerebroventricularly (icv) or intravenously (iv). Other similar sheep were given various doses of a CCK antagonist (loxiglumide) by the same routes. Bolus iv administration of either 35 micrograms or 200 micrograms of CCK had no effect on plasma GH levels. When given icv, however, CCK resulted in a marked (P less than 0.01) prolonged depression in plasma GH levels. The decrease in GH secretion could be partially attenuated by concurrent administration of loxiglumide, but was completely unaffected by concurrent administration of antisomatostatin serum icv. Loxiglumide alone had no effect on plasma GH levels when given at up to 200 micrograms icv, but intravenous administration of 8 mg of the CCK antagonist resulted in an increase in plasma GH concentrations (P less than 0.05). Plasma levels of somatostatin, glucose and cortisol were unaffected by both icv and iv administration of CCK. These results show that CCK can have a strong GH-inhibiting effect in the brain. Furthermore, this effect seems to be independent of hypothalamic somatostatin, suggesting another GH-inhibiting system exists.