Effects of Verapamil on Diurnal and Thyrotropin-Releasing Hormone-Stimulated Prolactin Levels in Man

The effects of the calcium entry blocker verapamil on the 24-h profile of PRL secretion and on the PRL response to TRH were investigated in six healthy volunteers. Verapamil (120 mg, three times daily) was administered orally for 1 week. In all subjects both basal and TRH-stimulated PRL levels were markedly elevated by verapamil. The average diurnal PRL concentration was increased from 13.0 +/- 2.0 micrograms/L to 25.2 +/- 4.4 (mean +/- SE; P = 0.02). Diurnal rhythm and pulsatility of PRL secretion were seen both before and during verapamil administration. Mean peak PRL concentrations after TRH injection (200 micrograms, iv) were significantly increased from 72.6 +/- 11.6 to 115.2 +/- 16.8 (P less than 0.01), and the mean area under the PRL concentration-time curves from 4332 +/- 962 micrograms/L.120 min to 6975 +/- 1334 (P = 0.01). The data are in striking contrast with previous findings from in vitro studies where verapamil has been reported to block calcium-mediated stimulus-secretion coupling and inhibit hormone secretion from pituitary cells. Interference with other PRL-regulating mechanisms may account for the demonstrated verapamil-induced PRL secretion in vivo.