Zinc chelation enhances thyroid hormone induction of growth hormone mRNA in GH3 cells

Abstract

The effects of restriction and addition of zinc on thyroid hormone responsiveness of the growth hormone gene were investigated in GH3, rat pituitary tumor cells. Addition of diethylenetriaminepenta-acetic acid (DTPA), a membrane-impermeable chelator, resulted in up to 10-fold increases in GH mRNA in the presence of 10 nM T3, with half-maximal induction at 50 μM DTPA. Only minor effects were seen in the absence of T3. Addition of zinc inhibited the stimulatory effect of DTPA in a dose-dependent manner. Equimolar concentrations of other divalent cations could not substitute for zinc, though inhibitions of the DTPA effect were observed at higher concentrations. In the absence of DTPA, exogenous zinc (100 μM) inhibited T3-induced GH mRNA by ≈33%. Addition of DTPA or zinc did not affect T3 binding to its nuclear receptor. DTPA also enhanced the stimulatory effect of dexamethasone on GH mRNA. The results demonstrate that restricted zinc availability positively affects T3 induction of the GH gene in GH3 cells.