Prolactin unresponsiveness to repeated sulpiride administration in man: recent findings

Abstract

The mechanism of prolactin (PRL) unresponsiveness to repeated sulpiride (SUL) administration was investigated by means of two experimental protocols. The first one was carried on in seven male volunteers (age 24 to 34 yr) and consisted of two phases separated by a 5-day interval. In both phases 1 mg/kg of SUL was given im and repeated, 24 h later, together with either placebo (PL, 2 ml saline iv) or TRH (200 µg iv). 7–10 days later a standard TRH test (200 µg iv) was performed. In the second protocol the usual dose (1 mg/Kg im) of SUL was administered alone and, 24 h later, together with 0.1 U/Kg iv of insulin (insulin tolerance test: ITT) to six male volunteers (age 20 to 32 yr). A control standard ITT (0.1 U/Kg iv) was also performed 7–10 days later. Plasma samples for the evaluation of PRL were taken in basal conditions and at regular intervals after each drug administration. In the first protocol, PRL shQwed a significant increase (peak values at 30 min) after SUL administration in both phases (phase A: 54.8 ± 5.6 ng/ml, mean ± SE vs 6.4 ± 0.3, p < 0.001. Phase B: 77.5 ± 3.9 vs 7.0 ± 0.6, p < 0.001). Twenty-four h later, PRL levels were still higher than basal and were not affected by the administration of SUL + PL or SUL + TRH. Also in the second protocol, SUL alone induced a significant PRL increase (peak values at 30 min: 47.1 ± 7.2 vs 4.2 ± 0.5, p < 0.005). Twenty-four h later PRL levels were still higher than in basal conditions (12.4 ± 1.5, p < 0.01 vs day one) and were modified by SUL + ITT administration only mildly (at 60 min: 17.0 ± 2.8, p < 0.05 vs basal) and significantly less than what observed after SUL and insulin alone (p < 0.005, p < 0.05, respectively). SUL then seems to induce a prolonged unresponsiveness of pituitary PRL secreting cells to multiple administration apparently not overcome by different stimuli (TRH, ITT), probably due to an alteration distal to the dopamine receptor.