Central nervous system-mediated stimulation of prolactin secretion by cimetidine, a histamine H2-receptor antagonist: impaired responsiveness in patients with prolactin-secreting tumors and idiopathic hyperprolactinemia.

Studies were performed to elucidate the mechanism by which cimetidine, a histamine H2-receptor antagonist, stimulates PRL release and to determine whether altered responsiveness exists in patients with PRL-secreting tumors and idiopathic hyperprolactinemia. The iv injection of cimetidine (300 mg) resulted in an acute rise of plasma PRL in all normal subjects, with peak values occurring at 7.5 or 15 min, followed by a return toward baseline. Responses were greater in females than in males and tended to be increased during the luteal phase of the menstrual cycle. A similar stimulatory effect on PRL secretion was demonstrated in unanesthetized, unrestrained rats. Cimetidine did not, however, stimulate PRL release or impair the PRL-suppressive effects of dopamine in primary monolayer cultures of dispersed rat adenohypophyseal cells. Diphenhydramine, a histamine H1-receptor antagonist, did not suppress the PRL response to cimetidine. Enhancement of dopaminergic tone peripherally (with L-dopa) but not centrally...