Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 μg/kg · min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 μg/kg · min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 μg/kg · min DA TRH (200 μg, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 ± 4.0%, mean ± SE) and hyperprolactinemic patients (-48.2 ± 5.5) was observed in response to 0.1 μg/kg · min DA. In normal cycling women DA infusion significantly (P < 0.02) reduced the PRL response to TRH with respect to the basal TRH test (Δ PRL 45.0 ± 7.0 vs. 77.9 ± 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 μg/kg · min DA than in basal conditions in hyperprolactinemic patients, both in absolute (Δ PRL 91.8 ± 17.6 vs. 38.4 ± 6.8, P < 0.03) and per cent (198.5 ± 67.6 vs. 32.1 ± 7.5, P < 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase > 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients. PRL levels decreased by 33.4 ± 5.0% in normal cycling women during 0.02 μg/kg · min DA infusion, but such a DA infusion rate did not affect the PRL response to TRH in this group (Δ PRL 77.7 ± 12.6 in the basal TRH test, 83.2 ± 12.0 during DA). Finally, 0.02 μg/kg · min DA did not induce any significant reduction in PRL serum levels of hyperprolactinemic women (-4.6 ± 3.8% of baseline P < 0.001 vs. normal women) and did not modify the PRL unresponsiveness to TRH (Δ % PRL 38.9 ± 10.1 in basal conditions, 48.8 ± 14.6 during 0.02 μg/kg · min DA). The results demonstrate that PRL unresponsiveness to TRH in pathological hyperprolactinemia is not the expression of an intrinsic adenomatous lactotroph defect, but simply the result of an already overstimulated PRL secretion due to a defective DA inhibition of pituitary lactotrophs. The PRL response to a very low DA infusion rate (0.02 μg/kg · min) was significantly reduced in hyperprolactinemic patients, but the importance of this relative DA resistance in the development and/or maintenance of pathological hyperprolactinemia remains to be elucidated.