Further observations on the difference in the metabolism of histamine in male and female rats.

In young rats a sex difference in the daily output of free histamine in the urine did not become apparent until after the 26th day of life, when males exhibited a lower excretion. Castration increased the urinary free histamine in male rats but had little or no effect in females. Testosterone depressed the urinary free histamine in castrated male and female rats, but did not change the excretion in intact females. When [(14)C]-histamine was given by subcutaneous injection, the fraction of the dose appearing in the urine in the unchanged form followed closely the excretion of endogenous free histamine. Parallel changes were also seen in the amounts of [(14)C]-histamine excreted after injection of [(14)C]-(-)-histidine. Intact male rats methylated [(14)C]-histamine given by injection and [(14)C]-histamine formed in the body more efficiently than did castrated males and females. Testosterone increased the degree of methylation of injected [(14)C]-histamine and of [(14)C]-histamine formed in the body. It is suggested that androgenic hormones increase the rate of histamine methylation in the rat and that this effect provides a satisfactory explanation for the lower excretion of urinary histamine in male rats.