Tc. Crowe et al., DOWN-REGULATION OF THYROXINE-BINDING GLOBULIN MESSENGER-RIBONUCLEIC-ACID BY 3,5,3'-TRIIODOTHYRONINE IN HUMAN HEPATOBLASTOMA CELLS, The Journal of clinical endocrinology and metabolism, 80(7), 1995, pp. 2233-2237
A sensitive [(125)]-T-4 binding assay was used to measure serum T-4-bi
nding globulin (TBG) in 60 individuals selected on the basis of their
total circulating T-3 concentrations, and a relationship between TBG a
nd circulating thyroid hormone levels in humans was confirmed. There w
as a significant correlation between serum TBG and T-3 or free T-4 ind
ex. TBG secretion and TBG messenger ribonucleic acid (mRNB) production
were studied with a continuous culture of the human hepatoblastoma ce
ll line, HepG2. Cells were maintained in serum-free media For experime
ntal manipulations. The addition of 100 nmol/L T-3 to the cell medium
resulted in a time-dependent down-regulation of TBG mRNA to 33 +/- 6%
(+/- SD, n = 4) of untreated control levels by 24 h. Suppression of TB
G mRNA was first detectable at 8 h (57% of untreated control levels).
The effect of T-3 was dose-responsive, with half-maximal suppression o
f TBG mRNA occurring at a bioavailable T-3 concentration of approximat
ely. 30 pmol/L. The effect of T-3 on TBG mRNA was not caused by a chan
ge in mRNA stability. Proteins secreted by HepG2 cells bound T-4 with
an affinity identical to that of normal circulating TBG. Cell secretio
n of TBG was parallel to total protein secretion and consistent with a
TBG secretion rate of 50 ng/10(6) cells per day. Variations in the co
ncentration of secreted binding protein in the presence of T-3 corresp
onded to the changes observed in TBG mRNA. These data show that circul
ating TBG concentration is negatively correlated with total serum T-3
in vivo. The corresponding down-regulation observed between TBG mRNA a
nd secreted protein in HepG2 cells suggests that this effect is the re
sult of the action of T-3 on cellular TBG mRNA synthesis.