ROLE OF ORNITHINE TRANSPORT INTO MITOCHONDRIA IN UREA SYNTHESIS OF RATS TREATED WITH THYROID-HORMONE

The purpose of this study was to find whether or not the ornithine tra nsport into mitochondria regulated urea synthesis when the thyroid sta tus is manipulated. Experiments were done on three groups of rats: giv en 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without triiodothy ronine (T-3) treatment, treated with PTU+T-3 or receiving neither PTU nor T-3 (control). The urinary excretion of urea, liver concentration of ornithine and ornithine transport into isolated hepatic mitochondri a in rats given PTU + T-3 were significantly lower than in rats given PTU alone. Ornithine transport was significantly inhibited by the addi tion of lysine specifically. This response was achieved well within th e physiological concentration of lysine. Compared with rats given PTU without T-3 treatment, the liver concentration of lysine was significa ntly higher in rats treated with PTU+T-3 and control rats. Ornithine t ransport into hepatic mitochondria was closely correlated with the exc retion of urea. The results suggest that the greater ornithine transpo rt in the hypothyroid (PTU alone) rats is likely to stimulate urea syn thesis. A thyroid hormone-induced increase in lysine concentration may be at least partly responsible for the changes in ornithine transport into mitochondria.