Sex steroid sulfotransferases (ST) sulfurylate and thus inactivate estrogens or androgens, producing an androgenized or estrogenized state in the liver. The expression of diabetes in a number of animal models is sexually dimorphic and has been associated with steroidal states. Although the viable yellow (Avy) mutation produces an insulin-resistant obesity syndrome in mice of both sexes, only males develop chronic hyperglycemia. Hyperglycemia was rapidly induced in Avy/a females by dexamethasone (dex). This treatment completely suppressed both endogenous plasma corticosterone and hepatic corticosterone-binding globulin (CBG) mRNA within 24 h. Hyperglycemia in dex-implanted Avy/a females was accompanied by aberrant shifts in hepatic androgen/estrogen balance. This was effected by induction of estrogen sulfotransferase (EST) mRNA together with a > 10-fold increase in enzymatic activity. Similar dex-induced increases in androgen ST or phenol ST were not observed. Prior implantation of estrogen prevented development of hyperglycemia. The time-dependent spontaneous reversal of dex-induced hyperglycemia correlated with re-expression of CBG mRNA transcripts and reduced levels of EST transcripts and enzyme activity. Although dex-induced hyperglycemia was limited to Avy/a females, dex elicited hyperinsulinemia in lean α/α control mice of both sexes and exacerbated constitutive hyperinsulinemia in Avy/a males and females. In summary, dex-induced hyperglycemia in Avy/a females was associated with increased catabolism of hepatic estrogens mediated by induction of EST.
Dexamethasone-Induced Hyperglycemia in Obese Avy/a (Viable Yellow) Female Mice Entails Preferential Induction of a Hepatic Estrogen Sulfotransferase
- Views Icon Views
- Share Icon Share
Anne M Gill, Edward H Leiter, Jerry G Powell, Harry D Chapman, Terence T Yen; Dexamethasone-Induced Hyperglycemia in Obese Avy/a (Viable Yellow) Female Mice Entails Preferential Induction of a Hepatic Estrogen Sulfotransferase. Diabetes 1 August 1994; 43 (8): 999–1004. https://doi.org/10.2337/diab.43.8.999
Download citation file: