Antiglucocorticoids: in vivo assay and evaluation of cortexolone, progesterone, and 6-beta-bromoprogesterone.
In vitro antiglucocorticoids (cortexolone and progesterone) were evaluated as in vivo antagonists of dexamethasone-induced increases in liver tyrosine amino transferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TPO; EC 1.13.1.12), and glycogen deposition. Cortexolone antagonized the TPO and glycogen responses to dexamethasone in the liver of adrenalectomized rats but did not significantly influence the induced TAT activity. Progesterone, although toxic at levels approaching those used for cortexolone, was capable of antagonizing the glycogen increase. A new antagonist, 6 beta-bromoprogesterone, was found to be nontoxic and was more potent than cortexolone in blocking the TPO and glycogen responses. These results demonstrate that in vivo antiglucocorticoid activity can be evaluated and suggested significant differences between the sensitivity of TAT induction and that of glycogen or TPO.
D015065:17-Hydroxycorticosteroids / Q000494:pharmacology*; D000818:Animals; D003350:Cortodoxone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D011374:Progesterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000378:metabolism
D015065:17-Hydroxycorticosteroids; C012795:6-bromoprogesterone; D005938:Glucocorticoids; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008112:Liver Glycogen; D011374:Progesterone; D003907:Dexamethasone; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase; D003350:Cortodoxone