Thyroid hormones and 5'-deiodinase in rat brown adipose tissue during fetal life

Abstract

Brown adipose tissue (BAT) iodothyronine 5'-deiodinase (5'D) activities are very high during fetal life but decrease 10-fold a few hours before birth. Accordingly, BAT 3,5,3'-triiodothyronine (T3) concentrations are also very high. The temporal patterns of changes in BAT 5'-D and fetal plasma insulin are similar (and differ from the pattern for catecholamines) but are not superimposable. A causal role for insulin in the activation of fetal BAT 5'-D is therefore not supported by the data. Maternal thyroidectomy leads to a decrease in the total and relative weight of fetal BAT and to a 30-50% increase in BAT 5'-D activities; BAT thyroid hormone concentrations are essentially unchanged. Fetal hypothyroidism was induced by giving methimazole and resulted in a marked decrease of BAT thyroxine (T4) and T3 concentrations. This treatment increased BAT 5'-D activity only on day 21 of gestation, but no effect was observed on day 20. The fetal 5'-D response to thyroid hormones infused into the methimazole-treated dams was studied at 21 days of gestation. The increase in BAT 5'-D induced by methimazole treatment was prevented by T4 infused into control dams but not by T3. In fetuses from thyroidectomized dams, the pattern of 5'-D regulation by thyroid hormones was impaired. It is suggested that the high concentrations of thyroid hormones present in fetal BAT might participate in the general maturation and development of fetal BAT.

Inhibition of Iodothyronine 5′-Deiodinase by Iopanoic Acid Does Not Block Nuclear T3 Accumulation During Rat Fetal Development

“…Our results are in agreement with published data of T3 and T4 concentrations in fetal tissues, which also increase during this period, coinciding with the onset of active fetal thyroid function (31)(32)(33). Interestingly, both cellular (31) and nuclear T3 levels are higher in fetal IBAT than in the other tissues.…”

Mitochondrial Biogenesis and Thyroid Status Maturation in Brown Fat Require CCAAT/Enhancer-binding Protein α

“…Thyroid Hormone Content and Iodothyronine 5Ј-Deiodinase Activity-Determination of tissue T 3 content and iodothyronine 5Ј-deiodinase activity were carried out as previously described (8). Because of the small amount of interscapular BAT during fetal life, determination of T 3 content required pools of 2-4 tissues/sample.…”

“…However, since innervation is not fully developed in the fetus (2,3), other biological factors are expected to be involved in determining brown fat differentiation, including the onset of UCP1 gene transcription. Potential candidates as regulatory factors are thyroid hormones, since complete maturation of BAT thyroid status is achieved during late fetal development (6), due to a high activity of type 2 iodothyronine 5Ј-deiodinase (D2) necessary for local generation of active thyroid hormone T 3 (7,8). Moreover, there is general agreement on the involvement of T 3 in controlling mitochondrial biogenesis, although the molecular mechanisms responsible are not well characterized (9).…”

Insulin increases the adrenergic stimulation of 5′ deiodinase activity and mRNA expression in rat brown adipocytes; role of MAPK and PI3K

“…High specific activity 125 I-T 4 (>3000 µCi/µg) was obtained in our laboratory with chloramine T and T 3 as substrate (Obregón et al 1989, Hernández & Obregón 1996. Before each assay, 125 I-T 4 was purified by paper electrophoresis to separate the contaminating iodide.…”

“…D2 activities were determined in homogenates by measuring the release of iodide, by the method previously described ) with modifications (Obregón et al 1989), using as final concentrations 2 nM T 4 (50 000 c.p.m. 125 I-T 4 ), 1 µM T 3 , 50 mM DTT, 1 mM PTU and 80-100 µg protein/100 µl total volume, pH 7·0, for 1 h at 37 C. Cell homogenates were tested in triplicates, using 2-3 culture flasks per treatment.…”