GENE-EXPRESSION AND SERUM THYROXINE-BINDING GLOBULIN ARE REGULATED BYADRENAL STATUS AND CORTICOSTERONE IN THE RAT

Supraphysiological doses of glucocorticoids reduce serum T4-binding gl obulin (TBG) concentrations when administered to human subjects. Studi es were performed in rats to determine if glucocorticoid administratio n alters serum TBG in another species, if circulating concentrations o f glucocorticoids tonically affect serum TBG concentrations, and if ch anges in TBG production are likely to be a cause of the glucocorticoid -induced changes in serum TBG concentrations that are observed in huma ns. The serum TBG-binding capacity was 14.9 +/- 2.3 nmol/liter in adre nalectomized male rats compared to 6.6 +/- 1.0 nmol/liter in intact ma le rats and 4.8 +/- 0.9 nmol/liter in adrenalectomized male rats that received corticosterone in a dose equal to or less than the replacemen t dose, as assessed by thymus weight (P < 0.01 for serum TBG in adrena lectomized vs. intact or adrenalectomized corticosterone-treated group s). Hepatic TBG mRNA content, as assessed by polymerase chain reaction amplification and expressed as a ratio of beta-actin mRNA content, wa s 0.10 +/- 0.03 density units in intact male rats, 0.59 +/- 0.17 densi ty units in adrenalectomized male rats, and 0.05 +/- 0.02 density unit s in adrenalectomized corticosterone-treated male rats (P < 0.03 for a drenalectomized vs. intact or adrenalectomized corticosterone-treated rats). Adrenalectomy increased the serum TBG-binding capacity in femal e rats (intact female rats, 13.9 +/- 1.0 nmol/liter; adrenalectomized female rats, 39.0 +/- 6.4 nmol/liter; P < 0.01). These studies indicat e that serum TBG is tonically down-regulated by adrenal glucocorticoid s, because corticosterone decreases the TBG production rate, probably at the level of transcription. This effect is similar to that describe d for corticosterone-binding globulin, but differs from that for many proteins of the serine protease inhibitor family that are related to T BG.