Alterations in cyclic AMP, intermediary metabolism, and ultrastructure in dog thyroid gland induced by synthetic double-stranded RNA

Abstract

The effects of in vivo administration of polyriboinosinic-polyribocytidylic acid [poly(rI:rC)], an interferon inducer, on cyclic AMP levels, [1- 14C]glucose oxidation, [ 32P]orthophosphate incorporation into phospholipids, release of 131I-labeled thyroid hormones, and ultrastructure were studied in the dog thyroid gland. After in vivo treatment with poly(rI:rC), the responsiveness of these parameters to TSH was evaluated in vitro. In poly(rI:rC)-treated animals, basal cyclic AMP levels were not significantly changed and basal [1- 14C]glucose oxidation was significantly inhibited. TSH increased cyclic AMP levels somewhat less in poly(rI:rC)-treated animals than in controls and stimulated [1- 14C]glucose oxidation in controls, but not in poly(rI:rC)-treated dogs. 32P Incorporation into phospholipids, on the other hand, was stimulated after poly(rI:rC) and it was further stimulated by TSH. In studies of specific phospholipid incorporation, both poly(rI:rC) and TSH responses were most prominent in the phosphatidylinositol and phosphatidylserine fractions. Poly(rI:rC)-treated thyroids showed increased basal release of total 131I with a marked relative increase in T 3 release. The responsiveness of I −, T 4, and T 8 release to TSH remained intact. Ultrasructural response to poly(rI:rC) included a marked dilatation and development of the rough endoplasmic reticulum and an increase in lysosome formation. After exposure to TSH, thyroid slices from poly(rI:rC)-treated dogs partially failed to develop pseudopods and colloid droplets. Poly(rI:rC) effects were present in normal dogs as well as in dogs in which endogenous TSH was suppressed. These findings suggest that poly(rI:rC) directly affects the dog thyroid gland.