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Histaminergic Regulation of Prolactin Secretion: Dose-Response Relationship and Possible Involvement of the Dopaminergic System^*

Department of Surgical Gastroenterology 235, Hvidovre Hospital, University of Copenhagen Copenhagen, Denmark

Address all correspondence and requests for reprints to: U. Knigge, M.D., Department of Surgical Gastroenterology 235, Hvidovre Hospital, University of Copenhagen, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.

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 g/kg BW.h to six normal men stimulated PRL secretion in a dosedependent manner [absolute change in PRL (PRL) area = 52 x (HA dose) – 618; r = 0.9926; P < 0.001]. The stimulatory effect of HA was modest andoccurred during the second hour of infusion. This increase might be due to the opposing effects ofHA on PRL secretion, specifically stimulation via Hi receptors and inhibition via H2 receptors. The PRL-releasing effect of 11 ng HA dihydrochloride was not significantly different from that of anequimolar dose of HA diphosphate (18 µg).

Selective activation of H2 receptors by combined infusion of HA and the HI receptor antagonist mepyramine inhibited PRL secretion compared to the effect of NaCl [APRL, –55 ± 23 (± SEM) VS. –20±17µIU/ml; P < 0.01; n = 6). Mepyramine infused alone had no effect (APRL, –43 ± 22 vs. –33 ± 30 µIU/ml; n = 6). Selective activation of Hi receptors by combined infusion of HA and the H2 receptor antagonist cimetidine stimulated PRL secretion (PRL, 193 ± 40 vs. –20 ± 17 µµlU/ml; P < 0.0005; n = 6). When infused alone, cimetidine had only a modest and late stimulatory effect (APRL, 35 ± 22 vs. –27 ± 15; P < 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 (PRL, –374 ± 70 vs. –184 ± 107 µIU/ml; P < 0.01; n = 6), whereas the PRL-stimulating effect of HI receptor activation was abolished by the drug (PRL, –249 ± 64 vs. –174 ± 54 µIU/ml; n 6). The latter effect of MET was not due to exhaustion of the lactotrophs, since 200 µg TRH stimulated PRL secretion during MET treatment.

These findings suggest that the HI receptor-mediated PRLstimulating effect of HA occurs through an inhibition of the dopaminergic system, whereas the H2 receptor-mediated PRLinhibiting effect of HA does not involve dopaminergic neurons.

^* This work was supported by grants from the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands, and Greenland (no. 24/81 and 38/83); the Danish Medical Research Council (no. 12-5665); the Gerda and AAge Haensch Foundation; and the Danish Insurrance Society, Borgen-Grants.

Received May 14, 1985.