Streptozotocin-induced diabetes and glucocorticoid receptor regulation: tissue- and age-specific variation.
Streptozotocin (STZ) -induced diabetic effects were analyzed for glucocorticoid receptor (GR) level and for in vitro activation of GR by specific binding analysis, using [3H]dexamethasone, a synthetic glucocorticoid, and by DNA cellulose and nuclear binding assay, in the liver and kidney of 15- (immature) and 120-day-old (mature) male mice. Comparison of GR level (fmol/mg protein) among the control mice reveals decreased (22-33%) specific binding in the liver and kidney of mature mice compared with immature ones. Scatchard analyses, however, reveal no change in the affinity (K(d)) of receptor at these two ages of mice. STZ-induced diabetes did not alter the level of GR in either of the tissues at both the ages studied. The GR from both the tissues underwent thermal activation, albeit the extent of activation was more pronounced in mature liver compared to immature, with no such difference of activation in the kidney. In diabetic mice, the activation of hepatic GR exhibits reduced DNA cellulose ( approximately 20-23%) and nuclear (24-30%) binding compared to control mice. In contrast, thermal activation of kidney GR does not show marked differences in diabetic mice at either of the ages studied. Cross-mixing experiments (i.e. binding of activated GR from diabetic mice to nuclei of control and vice-versa) performed on the mature liver, indicate receptor specificity. These findings reveal tissue- and age- specific variations in the level of GR that is not influenced under diabetic conditions. However, the activation of hepatic GR is reduced during STZ-induced diabetes that might play a role in controlling glucose homeostasis in diabetic animals.
Ranhotra
H S
HS
Department of Biochemistry, North-Eastern Hill University, 793 022, Shillong, India.
Sharma
R
R
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013311:Streptozocin
C033190:DNA-cellulose; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D013311:Streptozocin; D003907:Dexamethasone; D002482:Cellulose; D004247:DNA