Search

In glial cell cultures, iodothyronine 5'-deiodinase type II is stimulated by dibutyryl cAMP. Serum-free medium increases enzyme activity and prolongs the half-life of the enzyme. T4 and rT3 specifically inhibit this activity. We tested whether enzyme inactivation by T4 was mediated by changes in cytosolic free calcium concentration and/or phospholipid turnover. Intracellular calcium concentration was decreased either by chelation of extracellular calcium or by chelation of extracellular and intracellular calcium. Neither basal hypothyroid 5'-deiodinase activity nor its inactivation by T4 were modified in such experimental conditions, compared with control cells incubated in normal calcium-containing medium. T4 by itself had no effect on the cytosolic free calcium concentration for up to 20 min. Studies on phospholipid turnover included norepinephrine in parallel to T4 as positive stimulation control. While norepinephrine clearly accelerated phosphoinositide turnover, there was no effect of T4 on any phospholipid turnover. These results suggest that neither cytosolic free calcium nor phospholipid turnover is involved in T4-dependent modulation of 5'-deiodinase type II activity in astrocytes in culture.

Thyroid function was investigated in rats treated sc with a single injection of human recombinant interleukin-1 beta (hrIL-1). In 5 h 12.5 micrograms hrIL-1 decreased total serum T4 levels by 30 +/- 2% (P less than 0.01) and serum T3 levels by 35 +/- 4% (P less than 0.001). However free T4 and T3 fractions increased markedly within the first 140 min by 162 +/- 20% (P less than 0.001) and by 55 +/- 4% (P less than 0.001) resulting in a 88 +/- 20% increase in the free T4 concentration (P less than 0.001) but no increase in the free T3 concentration. Serum TSH concentration fell in the 5 h after the hrIL-1 injection by 77 +/- 3% (P less than 0.001). A similar decrease was observed with 0.125 micrograms hrIL-1. Five hours of starvation did not change serum TSH levels, suggesting that the effect of hrIL-1 on TSH was not due to decreased food intake. In order to test whether the decrease in serum TSH was due to an intrapituitary increase in T3, hrIL-1 was injected in hypothyroid rats: the fall of serum TSH was not prevented and it fell in 5 h from 14.05 +/- 0.56 to 9.66 +/- 0.98 ng/ml (31%, P less than 0.01, n = 14). These results suggest that hrIL-1 acts independently of thyroid hormones. Peripheral metabolism of T4 was studied by implanting [125I]T4 secreting minipumps during 14 days. There was no difference in T4 plasma clearance rate between control and treated animals. The fall of serum T4 was therefore explained by decreased secretion and not by increased catabolism since ether link cleavage of T4 and changes in hepatic deiodinase could not be detected. We therefore suggest that hrIL-1 inhibits thyroid function mainly at the hypothalamic-hypophyseal level.

The induction of hypothyroidism in rats by methimazole affects interscapular brown adipose tissue (IBAT) mitochondrial and peroxisomal enzyme activities in opposite directions. Hypothyroidism, indeed, decreases both mitochondrial succinate dehydrogenase and beta-oxidation total activities by 35 and 45%, respectively and increases peroxisomal catalase and acyl coenzyme A (acyl CoA) oxidase total activities 3.2- and 1.6-fold, respectively. Administration of a thyroid hormone analogue (3'-isopropyl-3,5-diiodo-L-thyronine) prevents these enzymatic modifications. The effects of hypothyroidism on IBAT mitochondrial enzyme activities seem to be direct, i.e. due to the lack of thyroid hormones, while those on peroxisomal enzyme activities might be indirect, i.e. secondary to the increased thermogenic needs of the rat and mediated by adrenergic stimulation. It is noteworthy that the indirect effects of hypothyroidism on peroxisomes are not observed in liver where acyl CoA oxidase activity is in fact decreased by 40%. In hypothyroid rat IBAT, administration of the peroxisome proliferator nafenopin does not further stimulate the already increased peroxisomal enzyme activities and does not inhibit the already decreased mitochondrial enzyme activities.