ALAN BALSAM, FRANKLIN SEXTON, AND SIDNEY H. INGBAR
Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth Israel Hospital, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215
ABSTRACT. In the present studies, we have evaluated the effects of fasting, variations in thyroid state, and interactions thereof on the kinetic properties of the microsomal enzyme in rat liver that generates T3 from T4. The formation of T3 from T4 (T3-neogenesis) in preparations of rat liver microsomes enriched with 10 mM dithiothreitol was monitored by assessing the formation of [I25I]T3 from [125I]T4 in the presence of various concentrations of stable T4. T3-neogenesis in this system was a saturable process that obeyed the laws of first order enzyme kinetics. The effects of diverse in vivo manipulations on the kinetics of T3-neogenesis were assessed. The Vmax was markedly decreased in preparations from thyroidectomized animals, being, respectively, partially and completely restored to normal with daily maintenance therapy with T4 (0.5 and 1.5 /μg/100 g BW) and markedly increased after the administration of supraphysiological replacement doses of T4 (5.0 μg/100 g-day). Km was not affected by alterations in thyroid state.
In experiments concerning the effects of fasting, cognizance was taken of the fact that hypothyroidism regularly evolves as a consequence of fasting. The Vmnx was decreased markedly, and Km was slightly decreased in preparations from intact rats fasted 72 h but not given physiological replacement with T4 or T3. In contrast, Vmax and Km were unchanged in hepatic microsomes from intact rats fasted 72 h but given daily parenteral replacement with T4 (1.5 μg/100 g) or T3 (0.5 /μg/100 g). These data demonstrate that hypothyroidism resulting from either thyroidectomy or fasting produces decreased intrinsic activity of the microsomal T4 5′-monodeiodinase. In contrast, fasting without concurrent hypothyroidism does not influence the intrinsic activity of the hepatic T3-neogenetic enzyme.
(Endocrinology 108: 472, 1981)