Intracellular protease activity in glucocorticoid-mediated thymolysis.
The effect of dexamethasone on rat thymus protease activity was tested by following hydrolysis of 14C-labeled globin. Most of the proteolytic activity was located in the cytoplasmic fraction obtained from either whole thymus homogenates or isolated thymic lymphocytes. The protease showed an acid pH optimum and was inhibited by pepstatin and leupeptin. The particulate fractions exhibited only a negligible proteolytic activity throughout the pH range tested. The administration of dexamethasone (9 alpha-fluoro-11 beta, 17,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione; 1 mg/kg, ip) to adrenalectomized castrated rats caused a marked increase in the acid protease activity assayed in the cytosol of whole thymus or thymic lymphocytes, with no change in the particular enzyme activity. The sensitivity of the cytosolic enzyme to several protease inhibitors was unchanged after glucocorticoid treatment. Minimal effective dexamethasone doses for thymic involution and increases in protease activity were 0.01 and 0.1 mg/kg BW, respectively. The half-maximal thymolytic effect was obtained at 0.05 mg/kg dexamethasone, while the half-maximal effect on the protease was observed only at 0.30 mg/kg dexamethasone. In contrast, in vitro exposure of isolated thymic lymphocytes to 8.3 X 10(-6) M dexamethasone failed to affect the acid protease activity in the cytosol, but produced a marked time-dependent cytolytic response. These observations suggest that glucocorticoid-induced cytolysis in rat thymic lymphocytes is not mediated by a direct effect of the hormone on endogenous proteases.
D000315:Adrenalectomy; D000818:Animals; D002369:Castration; D003907:Dexamethasone / Q000494:pharmacology*; D005914:Globins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D010436:Pepstatins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood*; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D013739:Testosterone / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects
D007976:Leupeptins; D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D013739:Testosterone; D003907:Dexamethasone; D005914:Globins; D010447:Peptide Hydrolases; C031375:pepstatin