ABNORMAL PROLACTIN RESPONSIVITY TO DOPAMINERGIC SUPPRESSION IN HYPERPROLACTINEMIC PATIENTS

Previous in vivo studies have shown that the constant infusion of dopamine suppresses prolactin (PRL) levels to within the normal range in a variety of hyperprolactinemic states, but there are no data on the relative suppressibility of the lactotroph in patients with hyperprolactinemia or on their metabolism of dopamine. Consequently, 6 patients with elevated PRL levels received a dopamine infusion of 4 .mu.g/kg per min to study PRL clearance while another 8 patients underwent a graded infusion at rates of 0, 1, 2 and 4 .mu.g/kg per min to test PRL suppressibility. In 4 patients of the latter group an 8 .mu.g/kg per min infusion rate was added. Healthy volunteer control subjects underwent comparable studies. PRL was measured by radioimmunoassay and dopamine by radioenzymatic techniques. The absolute PRL levels at each infusion rate were greater in the patients than in the control subjects. During the 4 .mu.g/kg per min infusion rate, the respective PRL concentrations were 8.2 .+-. 1.8 and 2.0 .+-. 0.1 ng/ml, (P < 0.001), despite higher dopamine levels in the patients (45.5 .+-. 6.7 vs. 33.5 .+-. 3.8 ng/ml, P < 0.05). Neither increasing the infusion rate to 8 .mu.g/kg per min nor prolonging the 4 .mu.g/kg per min infusion for 6 h decreased PRL levels further (9.6 .+-. 3.3 and 10.8 .+-. 2.5 ng/ml, respectively). Relative PRL resistance to dopamine in the hyperprolactinemic patients was demonstrated by a significantly more shallow slope of the regression line of PRL vs. dopamine concentrations and the concentration of dopamine causing 50% PRL suppression (14.7 vs. 6.8 ng/ml, P < 0.02). PRL metabolism was not disordered in the patients with elevated PRL levels, since the half-life (t 1/2) of the early phase of PRL clearance during their prolonged 4 .mu.g/kg per min dopamine infusion was similar to that present in the control subjectes (58.5 .+-. 5.9 vs. 53.7 .+-. 9.4 min). These data demonstrate both an absolute and relative lactotroph refractoriness to dopamine in hyperprolactinemic states and suggest that there remains either a dopamine-resistant cell population, and/or continued PRL release from an enlarged cell mass, despite maximal inhibitory dopamine concentrations.