+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Evidence of an altered 5' mono deiodinase for thyroxine in the liver of the fetal rabbit

Pediatric Research 15(8): 1123-1127

Evidence of an altered 5' mono deiodinase for thyroxine in the liver of the fetal rabbit

To explore further the factors that underly the deficient generation of 3,5,3'-triiodothyronine (T3) from thyroxine (T4) (T3-neogenesis) in fetal liver, studies were performed in homogenates and subcellular fractions of liver from pregnant rabbits and their corresponding fetuses. In whole homogenates, T3-neogenesis (percentage added T4:50 mg protein) during 3-h incubations of specimens from fetuses proceeded at a much slower rate (1.7 .+-. 0.5, mean .+-. SD) than in specimens from the corresponding does (1.4 .+-. 5.3). Dithiothreitol (DTT, 20 mM), a stimulant of T3-neogenesis, did not significantly alter the activity of fetal specimens (2.6 .+-. 1.3) but significantly increased activity in those obtained from does (18.2 .+-. 7.4). To investigate the basis for these differences, additional experiments were performed in which microsomal and cytosolic fractions from fetal and maternal livers were variously mixed and T3-neogenesis was assessed in the presence and absence of DTT. Activity of fetal microsomes was consistently less than in maternal microsomes, regardless of the source of the cytosols with which they were incubated. Mixtures containing fetal microsomes were not stimulated by DTT; those containing maternal microsomes were. In addition to this evidence of an abnormality with respect to the fetal enzyme, evidence was obtained of a concomitant abnormality in fetal cytosol fractions. Thus, T3-neogenesis by maternal microsomes was consistently greater when incubated with maternal cytosol than with fetal cytosol, presumably owing to lesser support of T3-neogenesis by cofactors present in cytosol. Additional evidence of an abnormality in the microsomal enzyme of the fetus was obtained in studies of the kinetics of T3-neogenesis. In the presence of DTT, derived values for the Km of the fetal enzyme were .apprx. 10-fold higher than were those for the maternal enzyme (5.9 .times. 10-5 and 7.1 .times. 10-6 M). Apparently, the defective generation of T3 from T4 seen in fetal liver from other species is also present in the liver of the fetal rabbit. Lower activity in the fetal liver is due in part to a lesser activity of cytosolic cofactors, but mainly to an abnormality in the T3-generating enyme, reflecting a lower concentration of enzyme and/or a lesser responsiveness to stimulatory cofactors. The enzyme in fetal liver than converts T4 to T3 behaves differently from that in maternal liver with respect to its affinity for substrate and its response to stimulatory SH cofactor. Fetal enzyme may be an isozymic variant of the adult enzyme, as has been reported for other hepatic enzymes. The relation between fetal and maternal enzymes may be analogous to that which exists with respect to enzymes of normal and malignant tissue.

(PDF 0-2 workdays service: $29.90)

Accession: 005411225

PMID: 7267187

Related references

Inhibition of rat thyroxine 5' mono deiodinase by propyl thio uracil relation to site of interaction of thyroxine and glutathione. Journal of Endocrinological Investigation 4(4): 379-388, 1981

Ontogenesis of iodothyronine-5'-deiodinase. Induction of 5'-deiodinating activity by insulin, glucocorticoid, and thyroxine in cultured fetal mouse liver. Journal of Clinical Investigation 74(6): 2254-2262, 1984

Dissociation of 5 deiodinase activities for thyroxine and 3 5 di iodo thyroxine in the fasted rat evidence for multiple enzymes and their sub cellular locations. 1980

Conversion of thyroxine to 3 3'5 tri iodo thyronine in rat liver the mechanism of stimulatory effects of thiols on thyroxine 5 deiodinase. Folia Endocrinologica Japonica 56(8): 1085-1095, 1980

Sub cellular localization of thyroxine and reverse tri iodo thyronine outer ring mono deiodinase activities. Clinical Research 26(2): 107A, 1978

Thyroxine and 3 3 5 triiodothyronine 5 deiodinase activities in the rat atria and ventricles in altered thyroid status. European Journal of Pharmacology 183(2): 286, 1990

The cDNA for the type I iodothyronine 5'-deiodinase encodes an enzyme manifesting both high Km and low Km activity. Evidence that rat liver and kidney contain a single enzyme which converts thyroxine to 3,5,3'-triiodothyronine. Journal of Biological Chemistry 267(18): 12539-12544, 1992

Plasma membrane a site for thyroxine and reverse tri iodo thyronine outer ring mono deiodinase activities. Clinical Research 26(3): 309A, 1978

Subcellular localization of thyroxine-5-deiodinase in rat liver. Journal of Endocrinological Investigation 3(1): 73-76, 1980

Evidence for a thyroxine deiodinating mechanism in the rat thyroid different from iodotyrosine deiodinase. Endocrinology 88(4): 918-923, 1971