Cimetidine effect of dopaminergic modulation of prolactin release in healthy women.
The aim of the present study was to test whether cimetidine (Cim) influences PIF (prolactin inhibitory factor), and thereby indirectly affects the release of prolactin (PRL) from the pituitary lactotrophs. For that purpose 10 mg metoclopramide (Met), known for its dopamine-receptor blocking properties, were first given orally to 6 subjects. This raised the PRL level from 13 +/- 2 to 97 +/- 12 ng/ml in 60 min (p less than 0.001). PRL tended to plateau at this level until 120 min. An additional 7 subjects were then injected iv with 400 mg Cim, 90 min after oral administration of placebo. Placebo did not change the basal PRL level, but the subsequent Cim injection raised the PRL level from 14 +/- 4 to 66 +/- 9 ng/ml (p less than 0.01). When, in the same subjects, an oral dose of Met was given (10 mg) PRL increased from 19 +/- 4 to 112 +/- 10 ng/ml (p less than 0.001). A subsequent Cim injection, given on top of the PRL plateau, 90 min after the Met ingestion, however, failed to induce any further increase in PRL. To exclude that this failure was not merely a reflection of a Met-induced depletion of the PRL stores, 25 micrograms thyrotropin-releasing hormone (TRH) were given iv to an additional 6 subjects, 90 min after ingestion of either placebo or Met. Also in these subjects placebo left basal PRL unaffected. The subsequent TRH injection, however, raised PRL from 10 +/- 2 to 55 +/- 6 ng/ml (p less than 0.001). Met increased PRL from 17 +/- 4 to 133 +/- 19 ng/ml (p less than 0.01) in these subjects, and TRH, subsequently injected, induced a further PRL increase to 174 +/- 18 ng/ml (p less than 0.01). The observation that Cim fails to elicit an increase in PRL after priming with Met thus indicates that Cim, under normal conditions, stimulates the PRL release via a reduced dopaminergic inhibition of the lactotrophs.
D000293:Adolescent; D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D008787:Metoclopramide / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*
D018492:Dopamine Antagonists; D006146:Guanidines; D002927:Cimetidine; D011388:Prolactin; D008787:Metoclopramide; D004298:Dopamine