Effects of Theophylline, Prostaglandin E₁and Adrenergic Blocking Agents on TSH Stimulation of Thyroid Intermediary Metabolism

Abstract

The effects of theophylline, pro-staglandin E1 and α and β-adrenergic blocking drugs on glucose oxidation and 32P incorporation into phospholipids and the TSH stimulation of these parameters have been studied in dog and pig thyroid slices. 5 × 10−3m Theophylline, which significantly inhibits phosphodiesterase, inhibited glucose oxidation and 32P incorporation into phospholipids. Lower concentrations of theo-phylline (5 × 10−5m) had no effect on these parameters and did not potentiate stimulation of them by TSH. Prostaglandin E1 (0.95 × 10−6m) significantly increased glucose-1-14C oxidation in dog thyroid slices but had no effect on 32P incorporation into phospholipid. Prostaglandin E1 neither inhibited nor potentiated the effects of TSH on 14CO2 production. Phenoxybenzamine (2.9 × 10−8m), an α-adrenergic blocking agent, did not modify basal or TSH stimulated glucose oxidation. DCI (1.15 × 10−4m), a β-adrenergic blocking agent, occasionally stimulated glucose oxidation but did not consistently reduce the effect of TSH. 3 × 10−5m Propranolol, another β-adrenergic blocking agent, did not influence basal glucose oxidation or the increase caused by TSH. At higher concentrations (3 × 10−4m) basal glucose oxidation was sometimes increased and TSH stimulation was consistently inhibited. This higher dose also abolished dibutyryl 3′,5′-cyclic AMP (DBC) enhanced glucose oxidation but had less of an effect on carbamylcholine stimulation. Glucose oxidation was not increased by ATP, ADP, AMP, or α-MSH. These results are discussed in relation to the hypothesis that TSH controls thyroid gland function via generation of 3′,5′-cyclic adenosine monophosphate. (Endocrinology84: 1082, 1969)