Sex difference in histamine metabolism in the rat

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

Female rats excrete much more free endogenous histamine than do males. The sex difference lies in histamine catabolism rather than biosynthesis, since females excrete, unchanged, a much higher percentage of injected histamine than do males. Investigation of the activity in vitro of the major histamine metabolizing enzymes, diamine oxidase (DAO) and imidazol-N-methyl transferase (IMT), showed no sex difference in distribution or activity, nor was there a sex difference in the activity of liver methionine-activating enzyme. Measurement of the biologic half-life of injected histamine revealed no sex difference in normal rats, in rats treated with the DAO inhibitor, aminoguanidine (AG), or in rats after nephrectomy, which removes almost all of IMT activity. A combination of AG and nephrectomy, however, resulted in a marked sex difference, which did not appear to be due to histamine conjugation or to liver drug-metabolizing enzymes. The findings suggest that male rats possess a minor histamine-metabolizing pathway which females lack.