title: Hormonal regulation of corticosteroid-binding globulin biosynthesis in the male rat.
abstract: Corticosteroid-binding globulin (CBG) is an acidic glycoprotein produced primarily by the liver and is the major glucocorticoid transport protein in rat blood. Various hormone treatments are known to modify plasma CBG levels and may thereby influence the bioavailability of glucocorticoids. We have, therefore, examined serum CBG and hepatic CBG mRNA levels in male rats after sc steroid (25 micrograms/100 g BW twice daily of dexamethasone, prednisolone, corticosterone, estrone, estradiol, ethinyl estradiol, progesterone, or 5 alpha-dihydrotestosterone) or T4 (10 micrograms/100 g BW twice daily) administration. After dexamethasone treatment, serum CBG levels decreased significantly (P less than 0.002) within 48 h and were 26% of those in vehicle-treated animals by 72 h. At this time, CBG mRNA was undetectable in liver RNA extracts by Northern blotting or solution hybridization, and nuclear run-off experiments indicated that dexamethasone reduces CBG gene transcription in the liver by at least 14-fold. Treatment with ethinyl estradiol also reduced serum CBG levels significantly (P less than 0.015) compared to pretreatment values. No other significant changes in serum CBG levels were observed after any other steroid hormone treatment, and alterations in hepatic CBG mRNA levels were only observed after dexamethasone treatment. T4 administration for 72 h increased serum CBG and hepatic CBG mRNA levels by 66% and 39%, respectively, but did not influence the rate of CBG gene transcription. Thus, increased CBG biosynthesis after thyroid hormone treatment appears to be due to an increase in CBG mRNA stability. No change in the Concanavalin-A-binding properties of CBG molecules was observed after treatment with either dexamethasone or T4, and this suggests that these hormones do not influence the type of oligosaccharide chains associated with this protein. We, therefore, conclude that dexamethasone and T4 regulate hepatic CBG biosynthesis in the rat by modulating CBG mRNA synthesis and stability, respectively.
authors.affiliation: Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Smith
authors.forename: G L
authors.initials: GL
authors.lastname: Hammond
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D006031:Glycosylation; D006728:Hormones / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013974:Thyroxine / Q000494:pharmacology*; D014156:Transcortin / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D006728:Hormones; D012333:RNA, Messenger; D003907:Dexamethasone; D014156:Transcortin; D013974:Thyroxine