Histaminergic regulation of prolactin secretion.

Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following systemic infusion of the amine. In addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1-receptors, while following systemic administration this effect is mediated via H2-receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional PRL stimulatory action not related to blockade of H2-receptors. This non-specific action is not exerted by the chemically different H2-receptor antagonist ranitidine. Since HA has no effect directly at the pituitary level, the actions of the amine may occur at different sites within the hypothalamus by an effect on hypothalamic transmitters regulating PRL secretion. Dopaminergic as well as serotoninergic neurons are involved in the mediation of the action of HA, since the dopamine (DA) concentration in the pituitary portal vessels is decreased by central or systemic infusion of HA, and since blockade of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta-endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation of the PRL response to HA. In men the effects of HA on PRL secretion are similar to the effects in male rats. Systemic infusion of HA stimulates PRL secretion via H1-receptors and inhibits PRL secretion via H2-receptors. The PRL-stimulatory effect of HA is caused by an inhibition of the dopaminergic system, while the PRL-inhibitory effect of HA may involve other transmitters than DA. In contrast to its stimulatory effect in men, HA had no effect on basal PRL secretion in women, but enhanced the PRL response to TRH. In rats or in humans the PRL stimulatory effect of HA is not caused by the cardiovascular actions of the amine.(ABSTRACT TRUNCATED AT 400 WORDS)