Inhibition of thyroxine 5′-deiodination type II in cultured human placental cells by cortisol, insulin, 3′,5′-cyclic adenosine monophosphate, and butyrate

Abstract

The regulation of conversion of thyroxine (T 4) to 3,5,3′-triiodothyronine (T 3) by the type II iodothyronine deiodinating pathway was studied in normal human placental cells cultured from the chorionic membrane. T 4 5′-deiodination was measured in cell sonicates after intact cells were incubated with test agents for 24 to 48 hours. Stimulation of T 4 5′-deiodination occurred to a similar degree after depriving cells of thyroid hormone in serum-free medium and in medium containing 10% calf serum. Cortisol at 10 to 100 nmol/L in serum-free medium inhibited T 4 5′-deiodination up to 36%, and 1 to 100 nmol/L of insulin inhibited deiodination up to 50%. Dibutyryl-cyclic AMP (dbcAMP) inhibited deiodination, but this appeared to result from the inhibitory effects of butyrate. Addition to the culture media of 8-bromo-cAMP, cholera toxin, and theophylline each caused partial inhibition of T 4 5′-deiodination, strongly suggesting an inhibitory effect of raised intracellular cAMP. Neither α- nor β-adrenergic agonists had any effect when added to the culture medium, nor did glucagon or cysteamine. These results demonstrate a complex, multihormonal control of human placental type II iodothyronine deiodination, and suggest that changes in the activity of this pathway may result in altered intracellular, and conceivably circulating, T 3 concentrations in states of cortisol excess and marked hyperinsulinism. The factor that regulates type II deiodination via cAMP remains to be identified.