Induction of Insulin-dependent Diabetes by Streptozotocin Inhibition by Estrogens and Potentiation by Androgens

Susceptibility of mice to experimental insulin-dependent diabetes as induced by multiple subdiabetogenic doses of streptozotocin has been shown to be strongly gender-dependent, males being much more susceptible than females. We examined this gender difference further in two strains of genetically susceptible mice to determine whether exogenous steroid sex hormones can both suppress the high susceptibility of males and potentiate the low susceptibility of females. Our results show that, in both BALB/cBOM and C57BL/6 mice, exogenous estrogens can suppress the high susceptibility of males. Conversely, the normally streptozotocin-resistant females become as highly susceptible as males after the administration of androgens. The inhibitory effect of estrogens and the potentiating effect of androgens can be demonstrated after the hormones are given to the mice either chronically (in slow-release capsules implanted at a subcutaneous site), or immediately prior to streptozotocin injection. These observations are consistent with the view that the critical factor that determines the susceptibility of mice to the hyperglycemic effects of streptozotocin is not the absolute concentration of androgens per se, but rather the relative overall level of androgens over estrogens in the recipient animal. Several alternative mechanisms for the effect of sex hormones on diabetogenic sensitivity are discussed.