Selenium deficiency and type II 5'-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine.
Selenium deficiency in rats is characterized by elevated serum T4 and decreased serum T3 concentrations, and low liver type I (5'D-I) and brain type II (5'D-II) iodothyronine 5'-deiodinase activities. These findings are partially explained by the demonstration that type I 5'D is a selenoprotein; however, 5'D-II does not contain selenium. Since 5'D-II varies inversely with serum T4 concentrations, and serum T4 is elevated in selenium deficiency, the decreased cerebrocortical 5'D-II activity may be secondary to the increased serum T4 levels. To determine the mechanism(s) by which selenium influences 5'D-II activity, we examined the effects of altered selenium intake on brain 5'D-II levels and enzyme turnover in euthyroid and thyroidectomized rats. Rats were fed a selenium-supplemented or selenium-deficient diet for 5 weeks from weaning; half of the animals were also thyroidectomized 3 weeks before death. Selenium deficiency was confirmed by decreased liver and brain glutathione peroxidase activities. In euthyroid rats, selenium deficiency caused a 38% increase in serum T4, and 91% and 39% decreases in 5'D-I and 5'D-II, respectively, compared to those in selenium-supplemented rats. In the thyroidectomized hypothyroid rats, selenium deficiency caused a 60% decrease in 5'D-I, but had no effect on 5'D-II activity, fractional turnover of the enzyme, or the calculated enzyme synthesis rate. The lack of effect of selenium deficiency on 5'D-II levels in hypothyroid rats is consistent with the finding that 5'D-II is not a seleno-enzyme. Thus, the decrease in brain and pituitary 5'D-II activity in selenium-deficient euthyroid rats is due to the T4-dependent increase in the turnover of the enzyme polypeptide.
Chanoine
J P
JP
Department of Nuclear Medicine, University of Massachusetts Medical Center, Worcester 01655.
Safran
M
M
Farwell
A P
AP
Tranter
P
P
Ekenbarger
D M
DM
Dubord
S
S
Alex
S
S
Arthur
J R
JR
Beckett
G J
GJ
Braverman
L E
LE
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007037:Hypothyroidism / Q000201:enzymology* / Q000209:etiology; D007453:Iodide Peroxidase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000502:physiology*; D014284:Triiodothyronine / Q000097:blood
D007527:Isoenzymes; D014284:Triiodothyronine; D013972:Thyrotropin; D007453:Iodide Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium; D013974:Thyroxine