Effect of dihydroergocristine administration on serum prolactin and growth hormone levels in normal, hyperprolactinaemic, and acromegalic subjects: further evidence for pituitary dopamine deficiency in these conditions

Abstract

Abstract. To evaluate further the pharmacological properties of dihydroergocristine in vivo, this drug (6 mg) or a placebo were administered orally on separate days to 11 healthy controls, 11 patients with adenomatous (n = 4) or idiopathic hyperprolactinaemia (n = 7), and 5 acromegalics with raised serum prolactin levels; serum prolactin (Prl) and growth hormone (GH) were measured at hourly intervals for 6 h. Dihydroergocristine induced a significant Prl decrease versus placebo in hyperprolactinaemics and acromegalics, but had no effect in healthy subjects. GH levels did not change in normals and hyperprolactinaemics, but decreased significantly in acromegalics. The Prl decrease induced by dihydroergocristine was significantly lower than that induced by l-dopa (500 mg po) in 9 hyperprolactinaemics so tested. Nomifensine (200 mg po) administered to 7 hyperprolactinaemics had no effect. Similarly, the GH decrease induced by the drug in acromegalics was significantly lower than that exerted by l-dopa, while nomifensine had no effect. Five hyperprolactinaemic patients were also given 12–18 mg dihydroergocristine daily for 3 months. There was evidence of partial or total Prl suppression and resumption of menses in all patients. These data indicate that dihydroergocristine is a relatively weak dopamine agonist at pituitary level and that oral doses, insufficient to exert Prl-lowering activity in normal subjects, are able to inhibit Prl and GH release in hyperprolactinaemics and dopamine-responsive acromegalics. These findings further support the existence of a 'denervation' supersensitivity to dopamine in these conditions, in which dopamine deficiency at pituitary level has been suggested on the basis of other experiments.