DEXAMETHASONE-INDUCED HYPERGLYCEMIA IN OBESE A(VY) A (VIABLE YELLOW) FEMALE MICE ENTAILS PREFERENTIAL INDUCTION OF A HEPATIC ESTROGEN SULFOTRANSFERASE/

Citation
Am. Gill et al., DEXAMETHASONE-INDUCED HYPERGLYCEMIA IN OBESE A(VY) A (VIABLE YELLOW) FEMALE MICE ENTAILS PREFERENTIAL INDUCTION OF A HEPATIC ESTROGEN SULFOTRANSFERASE/, Diabetes, 43(8), 1994, pp. 999-1004
Citations number
40
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
00121797
Volume
43
Issue
8
Year of publication
1994
Pages
999 - 1004
Database
ISI
SICI code
0012-1797(1994)43:8<999:DHIOAA>2.0.ZU;2-#
Abstract
Sex steroid sulfotransferases (ST) sulfurylate and thus inactivate est rogens or androgens, producing an androgenized or estrogenized state i n the liver. The expression of diabetes in a number of animal models i s sexually dimorphic and has been associated with steroidal states. Al though the viable yellow (A(vy)) mutation produces an insulin-resistan t obesity syndrome in mice of both sexes, only males develop chronic h yperglycemia. Hyperglycemia was rapidly induced in A(vy)/a females by dexamethasone (dex). This treatment completely suppressed both endogen ous plasma corticosterone and hepatic corticosterone-binding globulin (CBG) mRNA within 24 h. Hyperglycemia in dex-implanted A(vy)/a females was accompanied by aberrant shifts in hepatic androgen/ estrogen bala nce. This was effected by induction of estrogen sulfotransferase (EST) mRNA together with a > 10-fold increase in enzymatic activity. Simila r 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 lev els of EST transcripts and enzyme activity. Although dex-induced hyper glycemia was limited to A(vy)/a females, dex elicited hyperinsulinemia in lean a/a control mice of both sexes and exacerbated constitutive h yperinsulinemia in A(vy)/a males and females. In summary, dex-induced hyperglycemia in A(vy)/a females was associated with increased catabol ism of hepatic estrogens mediated by induction of EST.