Alterations in monodeiodination of iodothyronines in the fasting rat: Effects of reduced nonprotein sulfhydryl groups and hypothyroidism

Abstract

Hepatic monodeiodination of thyroxine (T 4), reverse triiodothyronine (rT 3), and triiodothyronine (T 3) are enzymic reactions that depend on tissue concentrations of sulfhydryl (SH) groups. Fasting in the rat is associated with low serum concentration of thyroid hormones (T 4 and T 3), a low rate of hepatic 5′-monodeiodination of T 4, and low tissue concentrations of nonprotein SH (NP-SH) groups. This study describes the relationship between these various abnormalities and the effect of fasting on conversion of rT 3 and T 3 to 3,3′-diiodothyronine (3,3′-T 2). Male Sprague-Dawley rats weighing 150–220 g were sacrificed after fasting for 0, 1, 2, and 4 days and iodothyronine monodeiodinations and total SH (T-SH) and NP-SH concentrations were quantified in liver homogenates. Hepatic T-SH concentration did not change appreciably during fasting. However, NP-SH levels decreased considerably at 1 day and then gradually recovered to or towards normal by 4 days of fasting. Hepatic NP-SH concentration in a representative experiment was 6.2 ± 0.20 μ M/g in controls and 4.1 ± 0.49, 5.2 ± 0.36, and 6.9 ± 1.2 μ M/g (mean ± SE) at 1, 2, and 4 days of fasting, respectively. On the other hand, T 4-T 3 converting activity (ng T 3 produced/μg T 4/geq tissue/hr) decreased progressively from 219 ± 15 in controls to 205 ± 18, 166 ± 6.7, ( p < 0.005) and 149 ± 10 ( p < 0.005) at 1, 2, and 4 days of fasting, respectively. Addition of dithiothreitol (DTT) to liver homogenates of 2-day (412 ± 15) and 4-day (397 ± 42) fasted rats did not render T 3 production from T 4 comparable to that in control animals (613 ± 76). When rats were treated with T 4 ( 2 μg 100 g body wt ), changes in liver NP-SH still occurred as mentioned. However, hepatic T 4-T 3 conversion was reduced (193 ± 11 versus 352 ± 29, p < 0.005) only at 2 days when NP-SH was low, and it increased normally after addition of DTT (691 ± 26 versus 823 ± 74, NS). It was normal in absence (357 ± 67) and in presence (872 ± 68) of DTT at 4 days of fasting when NP-SH was normal. Monodeiodination of T 3 to 3,3′-T 2 was normal in fasting, whereas that of rT 3 was low but normalized with DTT. The various data suggest that (1) low tissue NP-SH levels are important in causing the reduction in hepatic T 4 5′-monodeiodination only early in fasting (subsequently, hypothyroidism is the key factor); and (2) inner ring monodeiodination of T 3 is normal in fasting.