The effect of maturation, castration, and sex hormonal treatment on hepatic xanthine oxidase activity (XOA) was evaluated in Sprague-Dawley rats. In mature rats XOA was 59% greater in males than in females, whereas in the immature animal the differences between sexes were insignificant. Pubescence resulted in a twofold increase in activity in the male which was prevented by prepubertal orchiectomy. Conversely, prepubertal oophorectomy caused a twofold increase in XOA in females. Urinary uric acid excretion paralleled XOA in rats fed 1% oxonic acid. XOA was significantly elevated in females after postpubertal castration or testosterone treatment while orchiectomy or estradiol-17/? treatment in the mature male showed no effect. In summary, these data suggest that androgens are required during puberty for full expression of hepatic XOA, and furthermore, an ovarian suppressive effect is evident. In the adult rat only the female responds appreciably to hormonal manipulation.The influence of age and sex on the development of gout has been observed since ancient times (1). Population studies indicate that uric acid levels are lowest in childhood and diverge at puberty with female values about 1 mg/dl lower until menopause, at which time, the female values begin to approach male values (2-4). Wolfson et a1 attributed these variations to differences in the renal handling of uric acid, whereas more recent studies suggest either a permissive effect of androgens or an estrogen suppressive effect on blood urate values (5-In adult Wistar rats given short-term androgen or estrogen therapy, purine endproduct production was not significantly affected (1 1). Using prepubertal rats, Silverstein et a1 found age related increments in guanase and XOA although no sex differences were seen; moreover, adult enzyme activities were similar (1 2). No additional data are available regarding the effect of sex steroid hormones on uric acid production.A large body of information is available on the enzyme xanthine oxidase which catalyzes the conversion of hypoxanthine and xanthine to uric acid (13)(14)(15). Data on the induction of XOA by dietary protein manipulation in rats, allopurinol treatment of chicks, and enhanced urate precursor production by RNA and hypoxanthine feeding, and fructose infusion attest to the large number of potential factors controlling this particular enzyme.Because of the age and sex specific variations in urate concentration and the observed potential variability of XOA, we chose to reexamine the effects of gonadal tissue and exogenous sex steroid hormones on rat hepatic XOA. 10).
MATERIALS AND METHODSExperimental design. Sprague-Dawley rats were housed at room temperature in a light-dark environment and maintained on Purina chow and water ad libitum. Groups of