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 micrograms iv). 7-10 days later a standard TRH test (200 micrograms 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 showed 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 less than 0.001. Phase B: 77.5 +/- 3.9 vs 7.0 +/- 0.6, p less than 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 less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for dopamine-related and TRH-related pituitary TSH and PRL pools in patients with prolactinoma

“…However, our data support the possibility that tumour lactotropes in these patients are insensitive to dopami¬ nergic inhibition (12,13). It seems that defective dopaminergic inhibition on tumour lactotropes will further stimulate the tuberoinfundibular dopa- Plasma PRL levels in normal subjects were sig¬ nificantly elevated even 24 hours after the sulpiride injection, as was reported previously (14,15). This would suggest that the occupation of dopamine re¬ ceptors by sulpiride persisted over 24 hours.…”

“…Therefore, these results indicate the pres¬ ence of dopamine-related and TRH-related readily releasable TSH pools in normal thyrotropes of normal subjects and patients with prolactinoma, and also indicate the presence of dopamine-related and TRH-related readily releasable PRL pools in normal and tumour lactotropes. Why Bernini et al (14) could not observe a definite PRL response to sulpiride and TRH 24 hours after sulpiride injec¬ tion is not clear.…”