of Dopamine Signal in Different Subtypes of Human Growth Hormone- Secreting Adenomas*

This article reports the effect of dopamine (DA) on adenylyl cyclase (AC) activity and intracellular free calcium concentrations ([Ca”+]i) in 20 GH-secreting pituitary adenomas exclusively composed of somatotrophs (GH-omas) and 3 tumors largely constituted by mammosomatotrophs (MS-omas). DA (between 10 nmol/L and 100 rmol/L) did not reduce AC activity in any GH-omas, whereas the amine caused a significant inhibition in membranes from all MS-omas. The effect was detectable at DA concentrations higher than 0.1 pmol/L, and maximal inhibition (ranging from 24-30%) was reached at 10 pmol/L. The ergot derivative CH 29717 and l-sulpiride demonstrated potent agonist and antagonist activities, respectively. Somatostatin reduced AC activity in all tumors; the percent inhibition values (between 17-34%) were similar in GH-omas and MS-omas. In both GH-omas and MS-omas, DA (1 rmol/L) caused a significant [Ca”]i reduction (between 17-44%) that was essentially due to the block of Ca*+ influx from the extracellular snaces. The receptors involved in this effect showed the pharmacological properties of D2 receptors. In conclusion, the UA effect m tumoral somatotrophs is defective; DA fails to exert an inhibitory action on AC activity. In mammosomatotrophs, the typical D2 receptor-effector coupling is retained, resulting in decreased AC activity in these cells.