Histaminergic regulation of prolactin secretion: dose-response relationship and possible involvement of the dopaminergic system.
Histamine (HA) may participate in the neuroendocrine regulation of pituitary hormone secretion. HA diphosphate infused iv for 120 min in a dose of 9, 18, 30, or 50 micrograms/kg BW.h to six normal men stimulated PRL secretion in a dose-dependent manner [absolute change in PRL (delta PRL) area = 52 X (HA dose) - 618; r = 0.9926; P less than 0.001]. The stimulatory effect of HA was modest and occurred during the second hour of infusion. This increase might be due to the opposing effects of HA on PRL secretion, specifically stimulation via H1 receptors and inhibition via H2 receptors. The PRL-releasing effect of 11 micrograms HA dihydrochloride was not significantly different from that of an equimolar dose of HA diphosphate (18 micrograms). Selective activation of H2 receptors by combined infusion of HA and the H1 receptor antagonist mepyramine inhibited PRL secretion compared to the effect of NaCl [delta PRL, -55 +/- 23 (+/- SEM) vs. -20 +/- 17 microIU/ml; P less than 0.01; n = 6). Mepyramine infused alone had no effect (delta PRL, -43 +/- 22 vs. -33 +/- 30 microIU/ml; n = 6). Selective activation of H1 receptors by combined infusion of HA and the H2 receptor antagonist cimetidine stimulated PRL secretion (delta PRL, 193 +/- 40 vs. -20 +/- 17 microIU/ml; P less than 0.0005; n = 6). When infused alone, cimetidine had only a modest and late stimulatory effect (delta PRL, 35 +/- 22 vs. -27 +/- 15; P less than 0.025; n = 6). Dopamine receptor blockade with metoclopramide (MET; 10 mg, three times daily, orally) did not prevent the PRL-inhibiting action of H2 receptor activation (delta PRL, -374 +/- 70 vs. -184 +/- 107 microIU/ml; P less than 0.01; n = 6), whereas the PRL-stimulating effect of H1 receptor activation was abolished by the drug (delta PRL, -249 +/- 64 vs. -174 +/- 54 microIU/ml; n = 6). The latter effect of MET was not due to exhaustion of the lactotrophs, since 200 micrograms TRH stimulated PRL secretion during MET treatment. These findings suggest that the H1 receptor-mediated PRL-stimulating effect of HA occurs through an inhibition of the dopaminergic system, whereas the H2 receptor-mediated PRL-inhibiting effect of HA does not involve dopaminergic neurons.
D000328:Adult; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects
D011954:Receptors, Dopamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D011388:Prolactin; D011738:Pyrilamine; D008787:Metoclopramide