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