Title

The effect of zinc on thyroid hormone-induced growth hormone messenger ribonucleic acid levels in rat pituitary tumor cells

Date of Completion

January 1997

Keywords

Biology, Cell|Agriculture, Animal Culture and Nutrition|Health Sciences, Nutrition

Degree

Ph.D.

Abstract

Most of the physiological actions of thyroid hormones are mediated by binding of $3,5,3\sp\prime$-L-triiodothyronine (T3) to a specific class of nuclear receptor proteins, known as thyroid hormone receptors (TRs). The DNA binding domain of TRs contains highly conserved Zn-coordinated structures with cysteine residues which predict a structural and functional role of Zn for the receptors. In the present study, the requirement of Zn for the thyroid hormone responsiveness of the growth hormone gene has been investigated in a cell culture model, using diethylenetriaminepenta-acetic acid (DTPA), a cell impermeable chelator.^ DTPA profoundly stimulated T3-induced GH mRNA. Dosage-response studies showed about 10 fold induction of T3-induced GH mRNA at $\rm 400\ \mu M$ DTPA, with half-maximal stimulation at $\rm 50\ \mu M.$ In the absence of T3, the DTPA effect was marginal in nature. EDTA also enhanced T3-induced GH mRNA, but DTPA was more potent. Zn completely reversed the DTPA stimulation of T3-induced GH mRNA at a concentration at which seven other divalent cations tested (Cu, Cd, Co, Fe, Mg, Mn and Ni) were without effect. Zn alone, i.e., in the absence of DTPA, inhibited T3-induced GH mRNA by about 25-35%. DTPA also enhanced GH mRNA in the presence of 9 cis- and all trans retinoic acid as well as by dexamethasone.^ The effects of DTPA and Zn on nuclear uptake of radiolabelled T3 in GH3 cells were examined. Neither DTPA, nor Zn, affected nuclear uptake of radiolabelled T3. MT mRNA levels were examined in GH3 cells. Zn markedly induced MT mRNA levels in GH3 cells, both in the presence and absence of T3.^ The results show that despite the predicted requirement of Zn for T3 regulation of the growth hormone gene, Zn restriction positively affects T3-induction of GH gene in cultured rat pituitary tumor cells. ^