ZINC CHELATION ENHANCES THYROID-HORMONE INDUCTION OF GROWTH-HORMONE MESSENGER-RNA IN GH3 CELLS

The effects of restriction and addition of zinc on thyroid hormone res ponsiveness of the growth hormone gene were investigated in GH3, rat p ituitary tumor cells. Addition of diethylenetriaminepenta-acetic acid (DTPA), a membrane-impermeable chelator, resulted in up to 10-fold inc reases in GH mRNA. in the presence of 10 nM T3, with half-maximal indu ction at 50 mu M DTPA. Only minor effects were seen in the absence of T3. Addition of zinc inhibited the stimulatory effect of DTPA in a dos e-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, exogen ous zinc (100 mu M) inhibited T3-induced GH mRNA by approximate to 33% . Addition of DTPA or zinc did not affect T3 binding to its nuclear re ceptor. DTPA also enhanced the stimulatory effect of dexamethasone on GH mRNA. The results demonstrate that restricted zinc availability pos itively affects T3 induction of the GH gene in GH3 cells. (C) 1998 Els evier Science Ireland Ltd.