Prolactin-Secreting Adenomas in Women. VII. Dopamine Regulation of Prolactin Secretion*

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Abstract
Previous studies demonstrated that high doses of dopamine administered as a constant infusion were capable of suppressing PRL secretion in both normal and hyperprolactinemic individuals. The present study was designed to examine the dose-response relationship of PRL suppression to low doses of dopamine (between 0.06 and 4 μg/kg·min) infused in a stepwise fashion. Ten hyperprolactinemic patients with PRL-secreting pituitary adenomas and 10 normally menstruating women in the early follicular phase of a cycle were studied. For hyperprolactinemic women, the mean (±SD) serum PRL level (by RIA) was 112 ± 101 ng/ml, with a range of 26-386 ng/ml, the mean estradiol level (by RIA) was 28 ± 8 pg/ml, and the mean baseline dopamine level by carboxy-o-methyl transferase assay (COMT) was 357 ± 237 pg/ml (2.33 ± 1.54 × 10−9 M). The normal women had a mean PRL of 8.1 ± 3.5 ng/ml, a mean estradiol level of 42 ± 12 pg/ml, and a mean baseline dopamine level of 317 ± 223 pg/ml (2.07 ± 1.45 × 10−9 M). Concentrations of dopamine achieved at the lowest doses infused were less than 10 times baseline levels and were in the nanomolar range. The measured IC50 (the concentration of dopamine required to achieve 50% of maximal suppression) was 6 ± 3 × 10−9 M for normal women and 14 ± 4 × 10−9 M for hyperprolactinemic patients. The apparent inhibition constant determined by a nonlinear least squares procedure, was 3 ± 3 × 10−9 M for normal women and 11 ± 12 × 10−9 M for women with hyperprolactinemia. Both groups exhibited dose-dependent suppression of PRL to about 80% of initial values. Under these experimental conditions, the data do not support the hypothesis that there is a marked loss in sensitivity to dopamine in patients with PRLsecreting adenomas.

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