Effects of Cimetidine on Prolactin, Lh, and Sex Steroid Secretion in Male and Female Volunteers

Abstract

The histamine H2-receptor antagonist cimetidine, which has recently been introduced for the treatment of gastric and duodenal ulcers and haemorrhage, respectively, stimulates prolactin (PRL) secretion. The release of PRL after a bolus injection of the compound is significantly higher in female than in male volunteers, and is more pronounced during the luteal than during the follicular phase of the menstrual cycle. Oral administration of the drug stimulates PRL to a similar extent as parenteral administration. Treatment of male and female volunteers with cimetidine for 20 days (1 g/day orally) resulted in elevated serum PRL concentrations in both sexes. Basal LH levels as well as the response to 25 μg LH-RH were not significantly changed after treatment. Testosterone levels in males and oestradiol levels in females were not altered. Luteal progesterone, however, was significantly diminished in the menstrual cycles when cimetidine was given. The mechanism underlying the stimulatory effect of cimetidine on PRL secretion is not clear, but it does not seem that this ability is exerted via an inhibition of pituitary dopamine receptors. The dopaminergic effect of lisuride, an ergot alkaloid, could not be reversed by cimetidine.

Studies on the Role of Histamine in Human Pituitary Function

“…We have previously reported (Carlson & Ippoliti, 1977) and others have confirmed (Bohnet et al, 1978;Daubresse et al, 1978) that i.v. In man, evidence is strongest for a PRL-regulating role.…”

“…Experiments in animals and man have suggested that histamine may be an important regulator of pituitary hormone secretion. In addition to the demonstration of substantial concentrations of histamine and a histamine-sensitive adenylate cyclase in the hypothalamus (Kizer et al, 1976;Sat0 et al, 1974;Hegstrand et al, 1976), the administration of histamine or its antagonists has been reported to alter pituitary hormone release in rats (Libertun & McCann, 1976;Donoso et al, 1976;Arakelian & Libertun, 1977) and man (Carlson & Ippoliti, 1977;Pontiroli & Pozza, 1978;Bohnet et al, 1978;Pontiroli et al, 1976). The present studies were undertaken to explore further the role of histamine in the modulation of human pituitary function.…”

“…In addition to the demonstration of substantial concentrations of histamine and a histamine-sensitive adenylate cyclase in the hypothalamus (Kizer et al, 1976;Sat0 et al, 1974;Hegstrand et al, 1976), the administration of histamine or its antagonists has been reported to alter pituitary hormone release in rats (Libertun & McCann, 1976;Donoso et al, 1976;Arakelian & Libertun, 1977) and man (Carlson & Ippoliti, 1977;Pontiroli & Pozza, 1978;Bohnet et al, 1978;Pontiroli et al, 1976). In addition to the demonstration of substantial concentrations of histamine and a histamine-sensitive adenylate cyclase in the hypothalamus (Kizer et al, 1976;Sat0 et al, 1974;Hegstrand et al, 1976), the administration of histamine or its antagonists has been reported to alter pituitary hormone release in rats (Libertun & McCann, 1976;Donoso et al, 1976;Arakelian & Libertun, 1977) and man (Carlson & Ippoliti, 1977;Pontiroli & Pozza, 1978;Bohnet et al, 1978;Pontiroli et al, 1976).…”

Effects of Cimetidine on the Secretion of Some Pituitary Hormones

“…Our experiments showed that acute intra venous administration of cimetidine did not change the basal levels of the hormones exam ined and this is in accordance with data re ported by other authors (3,20). Apart from a non-significant increase in hTSH in response to TRH which suggests a further, more thorough investigation in a greater number of subjects to be performed, the only significant change was the increase in prolactin in response to TRH during the infusion of cimetidine.…”

Failure of Drugs Acting on H(2)-Receptors to Modify Plasma Prolactin Levels in Pituitary Adenomas: Evidence for a Suprapituitary Locus of Action

“…This response is more pro nounced in women than in men [2] and is dose-related [4]. In addition, we have shown that intravenous infusion of this drug also increases the prolac tin response to exogenous thyrotropin-releasing hormone (TRH) [17].…”