THYROID-HORMONES REGULATE DEVELOPMENT OF ENERGY-METABOLISM ENZYMES INRAT PROXIMAL CONVOLUTED TUBULE

Ketone bodies represent preferred energy substrates in the adult rat p roximal tubule. They are abundant in the plasma of suckling rats and m ight represent an important oxidative substrate for the immature proxi mal tubule. The postnatal development of two enzymes involved in keton e body oxidation pathway, 3-ketoacid-CoA transferase and acetoacetyl-C oA thiolase, and of citrate synthase and carnitine acetyltransferase w as studied in microdissected rat proximal convoluted tubule (PCT) at 1 , 8, 16, and 21 days after birth. The enzyme levels in PCT of juxtamed ullary and subcapsular nephrons were compared at 8, 16, and 21 days. A role of thyroid hormones in regulating the development of these enzym es was investigated by studying 8- and 21-day-old pups made hypothyroi d by propylthiouracyl (PTU) treatment, as well as 21-day hyperthyroid rats. PTU treatment had no effect on enzyme activities on day 8. In co ntrast, the activity of all mitochondrial enzymes, except acetoacetyl- CoA thiolase, was significantly decreased in 21-day-old hypothyroid pu ps. In hypothyroid animals, the normal development of 3-ketoacid-CoA t ransferase, citrate synthase, and carnitine acetyltransferase could be restored after treatment by triiodothyronine (T-3) In addition, one s ingle injection of T-3 to 8-day-old control pups induced a precocious rise in the activity of 3-ketoacid-CoA transferase, citrate synthase, and carnitine acetyltransferase in juxtamedullary PCT and in the activ ity of citrate synthase and carnitine acetyltransferase in subcapsular PCT. Altogether, these results point out the importance of the postna tal physiological rise in T-3 in triggering the development of some mi tochondrial oxidative enzymes in the PCT.