A new glucocorticoid receptor species: relation to induction of tryptophan dioxygenase by glucocorticoids.
When rats were treated with a high dose (greater than or equal to 20 micrograms/100 g BW) of dexamethasone, their liver cytosol showed a predominant peak of specific binding protein of glucocorticoid eluting with 0.13-0.14 M NaCl on diethylaminoethyl cellulose chromatography. On the other hand, when rats were treated with a low dose (approximately 2 micrograms/100 g BW) of dexamethasone, the cytosol showed only the same peak as that of untreated rats, which is widely thought to be that of the typical glucocorticoid receptor. The appearance of the new binding peak depended both on the dose of hormone and the time (from 30 min to 20 h) after dexamethasone treatment; it disappeared 40 h after treatment. A peak similar to that in the cytosol also appeared in the nuclear fraction after treatment with a high dose of hormone. The glucocorticoid-inducible enzymes, tryptophan dioxygenase [(TO) EC 1.13.11.11] and tyrosine aminotransferase (EC 2.6.1.5) were assayed as physiological markers of receptor function. TO induction correlated well with the appearance of the new binding peak in terms of dose- and time dependence on glucocorticoid, whereas tyrosine aminotransferase induction did not. The new peak of glucocorticoid-binding protein detected in the cytosol and nuclear fractions may thus represent the glucocorticoid receptor species involved in TO induction, physiological changes under stress, and pharmacological changes after therapy with high doses of glucocorticoid hormones.
Hirota
T
T
Hirota
K
K
Sanno
Y
Y
Tanaka
T
T
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002848:Chromatography, DEAE-Cellulose; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D006358:Hot Temperature; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000502:physiology*; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase