Involvement of hepatic glucocorticoid receptor-mediated functions in steroid-induced cataract formation.
Determination of whether the steroid-induced cataract formation is caused through glucocorticoid (GC) receptor-mediated process was conducted by using GC antagonist (RU486) and anti-GC receptor antibody, and by sucrose density gradient ultracentrifugation analysis. (1) When 15 day-old chick embryos were treated with dexamethasone (DEX, 0.025 micromol per egg), their lenses started to form an opaque ring around the peri-nuclear region (stage II-III) after 12 hr and developed into nuclear-like cataract (stage IV-V) after 44 hr. The cataract formation examined at the 44 hr could be effectively prevented by administration of RU486 (0.2 micromol per egg) ranging from 2 hr before to 12 hr after the DEX administration. (2) GC receptor was present in liver, but could not be determined in lens by western blot analysis using monoclonal anti-GC receptor antibody. (3) Sucrose gradient ultracentrifugation analysis indicated that the receptor (9S) in the liver could be transformed to the 4S form after 0.4M NaCl treatment. Combined with our previous data, this suggests that changes in hepatic functions mediated by the GC receptor after the GC administration may be involved in the process of the cataract formation.
Hamamichi
Shusei
S
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, 199-0195, Japan.
Kosano
Hiroshi
H
Nakai
Shinji
S
Ogihara-Umeda
Izumi
I
Nishigori
Hideo
H
D000818:Animals; D015153:Blotting, Western; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002499:Centrifugation, Density Gradient; D002642:Chick Embryo; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007908:Lens, Crystalline / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000276:immunology / Q000502:physiology*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone