Glutathione-dependent thyroxine 5'-monodeiodination modulates growth hormone production by cultured nonthyrotropic rat pituitary cells.

Abstract

Conversion of L-T4 (T4) to L-T3 (T3) was assessed in GH3 rat pituitary cells which secrete GH and PRL. We tested the hypothesis that 5′-monodeiodination of T4 by these cells was dependent on intracellular glutathione (GSH), as previously suggested for liver and kidney. The GSH content of sonicated pituitary cell homogenates was 40 nmol/mg protein. This sonicate catalyzed the 5′-monodeiodination, generating 0.92 ± 0.08 pmol T3/mg • h in the presence of 50 nM T4 and 1 mM dithiothreitol (DTT). After depletion of GSH by dialysis of the cell sonicate, no T3 was generated. The addition of GSH (10 μM) to the dialysate restored 5′-monodeiodinase activity. This showed the thiol dependence of the reaction. When intact cells were incubated overnight with intracellular GSH-depleting agents (diethylmaleate or diamide), the 5′-monodeiodination of T4 was abolished. Propylthiouracil (PTU; 5 μM) did not inhibit T4 to T3 conversion in the intact cells in monolayer culture or in the cell sonicate. In contrast, sodium ipodat...