Evidence for lactotroph dopamine resistance in idiopathic hyperprolactinemia

Previous studies in patients with idiopathic hyperprolactinemia (IH) that have suggested the presence of decreased central dopaminergic tone have assumed normal responsiveness of lactotrophs to dopamine (DA). We have examined DA sensitivity in 17 women with IH and 19 female controls by evaluating the plasma PRL responses to successive infusions of increasing concentrations of DA (4, 40, and 400 ng/kg . min) as well as to a dopaminergic agonist, bromocriptine (2.5 mg, orally), and to a dopaminergic agonist, bromocriptine (2.5 mg, orally), and to a dopaminergic receptor blocker, domperidone (2 mg, iv). PRL levels in controls were unchanged during a saline infusion, but decreased by 34 +/- 7% (mean +/- SE) at the end of the lowest DA infusion (P less than 0.05 vs. saline). Progressive PRL suppression was produced with each increasing dose. In contrast, in patients with IH, the lowest dose produced no significant suppression from basal PRL levels (P less than 0.001 vs. controls); at 40 ng/kg . min DA, fractional suppression was evident but was less than that in controls (P less than 0.01); at 400 ng/kg . min, fractional PRL suppression in IH patients was indistinguishable from that in controls (70 +/- 6% vs. 73 +/- 4%). Patients with IH also exhibited markedly reduced and delayed PRL response to domperidone (P less than 0.02 vs. controls). Significant impairment of the PRL-lowering effect of bromocriptine was observed in the IH patients between 1 and 2 h (P less than 0.02 vs. controls), and their responses to bromocriptine were again delayed. The results indicate the presence of a relative resistance to DA in patients with IH. This resistance is compatible with a decrease in the number or affinity of lactotroph DA receptors.