STIMULATION OF SEX HORMONE-BINDING GLOBULIN MESSENGER-RNA AND ATTENUATION OF CORTICOSTEROID-BINDING GLOBULIN MESSENGER-RNA BY TRIIODOTHYRONINE IN HUMAN HEPATOMA-CELLS

We examined the time course and dose response of the triiodothyronine (T-3) effect on mRNAs for sex hormone-binding globulin (SHBG) and cort icosteroid-binding globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure to a saturating dose of T-3, SHBG mRNA wa s unchanged but increased to 1.5+/-0.1 times the unstimulated control at 22 h. Maximal stimulation (2.3+/-0.6) was observed at 2-3 days. Cor ticosteroid-binding globulin mRNA was unchanged for 22 h after exposur e to T-3 but diminished thereafter to 64% by day 3. At 3-4 days of exp osure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the T-3 concentration. For both mRNAs, half-maximal response occur red between 10 and 20 pmol/l bioavailable T-3. Cortisol-binding protei ns secreted by HepG2 cells after 3 days in culture also were T-3 dose- responsive. No re-uptake of secreted CBG by the cells was observed, su ggesting that the T-3 effect on CBG secretion occurs during production of the mature protein. These data suggest that T-3 stimulates the exp ression of the SHBG gene and attenuates the expression of the CBG gene . The effects of T-3 On these genes are consistent with the increase i n circulating SHBG and decrease in circulating CBG observed in hyperth yroidism. The HepG2 cells may be a useful human cell line in which to study the diversity of the molecular mechanisms of T-3 action.