HI and H2 Histamine Receptor Participation in the Brain Control of Prolactin Secretion in Lactating Rats1

Abstract

The histaminergic regulation of prolactin secretion in the lactating rat and the possible involvement of H1 and H2 histamine receptors in this control were evaluated. Prolactin was measured by radioimmunoassay in blood samples withdrawn through an intrajugular silastic catheter from undisturbed lactating mothers 10-15 days after delivery. In some of those rats a stainless steel cannula was placed in the 3rd ventricle. The tested drugs, H1 and H2 receptor agonists and antagonists, were injected either by the intrasilastic route or intraventricularly immediately before the onset of suckling and after a basal sample was taken. New samples were withdrawn 10, 20, 30 and 60 min thereafter. Suckling caused a 12- to 18-fold increase in serum prolactin by 10 min in control saline-injected mothers. In non-suckled mothers (NSM) injected with saline, prolactin levels were low at all times. Systemic or intraventricular diphenhydramine and mepyramine, H1 receptor antagonists, suppressed the increment in prolactin observed in suckled mothers (SM). Intraventricular metiamide, and H2 receptor antagonist, did not modify prolactin secretion in SM but drastically increased serum prolactin in NSM. A small but significant increase in prolactin titers was observed in NSM injected intraventricularly with histamine. 4-Methylhistamine, an H2 agonist, was ineffective when used intraventricularly in NSM, but suppressed prolactin enhancement in SM. In lactating mothers, brain histamine probably has a dual control on prolactin secretion. H2 receptors mediate events related to inhibition of prolactin release, since the agonist 4-methylhistamine blocked the prolactin rise in SM, while the antagonist metiamide promoted release of the hormone in NSM. H1 receptors seem to be related to a facilitatory mechanism, since classical antihistamines suppress the serum prolactin increase that follows the onset of suckling, while histamine itself is able to release prolactin in NSM.