The Effect of Histamine and H₁and H₂Receptors on Prolactin and Luteinizing Hormone Release in Humans: Sex Differences and the Role of Stress

Abstract

The present experiments were performed to investigate the possible role of histamine and its receptors, H1 and H2, in the control of PRL and LH release in normal adult humans of both sexes. Histamine infusion (200 microgram, iv, in 15 min) induced PRL and LH release in men; in women, histamine inhibited LH release without affecting PRL release. Two H1 antagonists, dexchlorpheniramine (10 mg, iv) and promethazine (50 mg, im), reduced PRL release in both sexes, stimulated LH release in men, and inhibited LH release in women. Cimetidine, an H2 antagonist (400 mg, iv), elicited PRL release in both sexes, more consistently in females than in males, and was without effect on LH release in either sex. These data suggest that in humans, the effect of histamine on PRL release is linked to H1 and H2 receptors, which respectively stimulate and inhibit PRL release independently of sex. The effect of histamine on LH release appears to depend on sex and to be mediated only by H1 receptors. To rule out the possibility that the effects of histamine are merely due to a nonspecific stress reaction, we have evaluated PRL and LH release in otherwise normal men and women undergoing surgery for gallstones. Surgery was accompanied by PRL release in both sexes, more evident in women, and by LH release only in men. These results indicate that the effect of histamine on PRL and LH release in humans is linked to sex and H1 and H2 receptors and is not due to stress; further studies are required to clarify the possible mechanism and site of action of histamine in modifying PRL and LH release in humans.

Modulation of Basal and LRH-Stimulated Gonadotrophin Secretion by Histamine in Normal Men

“…In contrast a recent study in normal human males [17] showed a significant stimulation of the basal LH secre tion by an even lower dose of HA. This discrepancy is not readily explainable.…”

“…In ovariectomized estrogen/progesterone primed rats and in proestrus rats HA administered intraventricular ly stimulated LH secretion [5,13]. No effect of HA was found in estrus and diestrus rats [5],In humans, HA administered as an intravenous infusion was found to stimulate basal LH secretion in males and to inhibit basal LH secretion in females in the early follicular phase [17]. Intravenous injections of the H2-receptor anta gonists cimetidine (C) and ranitidine did not affect the go nadotrophin secretion [3,10], Long-term treatment with cimetidine has been found to increase basal as well as LRHstimulated gonadotrophin secretion [10,16,23], However, this stimulation is presumably caused by an anti-androgen effect of cimetidine rather than by a blockade of ^-recep tors [10,26].…”

Histamine-Induced Prolactin Release: Pharmacological Characterization of Receptors in Male Rats

“…It ap pears, therefore, that histamine might involve activation of H2-receptors to increase the release of prolactin. However, this view contrasts with a dual role of histamine postulated on the basis of results obtained with histamine agonists and antagonists which indicated inhibition through H2-receptors and stimulation of prolactin release through Hi-receptors [1,26]. Since the specificity of the histaminergic agents was not examined in the above-mentioned studies, it can be concluded that the identity of receptors mediating the his tamine effect on prolactin release remains unproven.…”

Estrogen Receptor Immunoreactivity Is Present in the Majority of Central Histaminergic Neurons: Evidence for a New Neuroendocrine Pathway Associated with Luteinizing Hormone-Releasing Hormone-Synthesizing Neurons in Rats and Humans1

“…Our current understanding of the role of histamine in the regulation of LH release in humans is restricted to a series of studies that predominantly involved H2 antagonists administered peripherally (48 -55); no H2 receptor-specific effects on circulating levels of LH have been demonstrated. In contrast, the reported effects of H1 antagonists include the suppression of LH in women and its elevation in men (50); paradoxically, comparable sex-dependent effects were achieved with peripherally administered histamine (50). Nevertheless, the H1 antagonist employed in another study (49) was without effect on LH levels in either sex.…”