Effect of thyroid hormone on cyclic AMP phosphodiesterase in rat kidney.

Abstract

Abstract-The effect of thyroid hormone on the activity of low Km cyclic AMP phos phodiesterase of the particulate fraction from the kidney was investigated.This enzyme activity increased in the cortex from hypothyroid rats and reverted to the normal level after the subcutaneous administration of L-3,5,3'-triiodothyronine (T3) daily for 3 days. However, this hormone did not affect the enzymes from the normal rats. In vitro experiments revealed that T3 as well as various known phosphodiesterase inhibitors similarly inhibited the activity of low Km cyclic AMP phosphodiesterase from both normal and hypothyroid rat kidneys. The results of the present study suggest that the effect of thyroid hormone on cyclic AMP phosphodiesterase was not direct but was mediated by a modulation of the rate of protein synthesis and an unknown mecha nism in the kidney.Cyclic AMP phosphodiesterase is the only known enzyme which metabolizes cyclic AMP to 5'-AMP. This enzyme is distributed ubiquitously in various tissues and species.Moreover, the activity of this enzyme is regulated by hormones such as insulin, glucagon and catecholamines (1-4).Hypothyroid rats lose the ability to respond to epinephrine (5-7). This phenomenon may be explained by changes in number and affinity of the receptors (8, 9), the reduced activity of adenylate cyclase (10) and the increased activity of low Km cyclic AMP phos phodiesterase (1l, 12), all of which have been observed in hypothyroid rat tissues. In our laboratory, the effects of adrenergic agonists on hypothyroid rat tissues were investigated by using the isolated atria and liver (13-15).We examined the relationship between cyclic AMP phosphodiesterase and thyroid status in the rat kidney and our findings are reported herein. MATERIALS AND METHODSMale Wistar rats were made hypothyroidic by feeding a 0.15% propylthiouracil diet for more than 12 weeks. Concentrations of L-3,5,3'-triiodothyronine (T3) and thyroxine in the serum markedly decreased in these rats, as described previously (16). Hypothyroid rats were given 50 ,€g of T3 per 100 g body weight s.c., daily x 3 and sacrificed 48 h after the last administration of T3. T3 concentration in the plasma was restored to normal or slightly higher values at this point of time.Preparation of cyclic AMP phosphodiesterase:The soluble and particulate fractions