|Cassar-Malek, I. - INRA, FRANCE|
|Picard, B. - INRA, FRANCE|
|Hocquette, J. - INRA, FRANCE|
Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 21, 2006
Publication Date: N/A
Interpretive Summary: Thyroid hormones (TH) play a crucial role in growth, development, and function of most vertebrate tissues, as shown previously for brain, bone, adipose tissue, and muscle. These hormones affect both tissue accretion and differentiation in the fetus by a combination of metabolic and non-metabolic mechanisms. Heart and skeletal muscles are important target tissues for TH action. Particularly, TH play an important role in normal development of skeletal muscle. It is generally assumed that developmental and metabolic effects of TH are mediated by triiodothyronine (T3), which is mainly produced by peripheral 5'-deiodination of thyroxine (T4) by 5'-deiodination. In the present study, we have examined the hypothesis that small, but significant changes in plasma concentrations of T4, T3, and reverse-T3 (rT3), and hepatic activity of type-1 5'-deiodinase (5'D1) might participate in the regulation of tissue differentiation before birth. For this purpose, we have developed a multivariate statistical analysis procedure in order to depict temporal relationships between thyroid status, tissue oxidative capacity, and muscle differentiation in bovine fetuses during the two last trimesters of gestation. From the second trimester onwards, plasma concentrations of T4, T3 and rT3 and hepatic 5'D activity increased with gestational age. During that time a positive correlation was shown between plasma T3 concentrations and mitochondrial enzyme activities in oxidative muscles but not in liver. Data suggest that the weak elevation of fetal plasma T3 concentrations in the last trimester could be sufficient to favor the differentiation of oxidative muscles.
Technical Abstract: Thyroid hormones play a crucial role in the development and metabolism of their target tissues. The temporal relationships between thyroid status (plasma concentration of thyroxine [T4], triiodothyronine [T3], reverse-T3 [rT3], and hepatic activity of 5'-deiodinase [5'D]) and tissue differentiation (liver, heart, and skeletal muscles) were examined in bovine fetuses using principal component analysis of the data. With regard to thyroid status and muscle differentiation, a clear discrimination of the fetuses according to their age was observed, especially near birth. From the second trimester onwards, plasma concentrations of T4, T3 and rT3 and hepatic 5'D activity increased with gestational age. High T4 and rT3, and low T3 concentrations were observed near term in spite of a mature hepatic 5'D activity. Muscle contractile and metabolic differentiation was demonstrated by the disappearance of fetal myosin heavy chain and by the increase in mitochondrial enzyme activities (citrate synthase and cytochrome c oxidase) at 260 days post-conception. Small changes were observed in the activities of these oxidative enzymes in liver. A positive correlation (r > 0.51, P < 0.01) was shown between plasma T3 concentrations and mitochondrial enzyme activities in oxidative muscles only (Masseter, Rectus abdominalis). Data suggest that the small but significant elevation of fetal plasma T3 concentrations in the last trimester was sufficient to favor the differentiation of oxidative muscles.