Developmental Control of Iodothyronine Deiodinases by Cortisol in the Ovine Fetus and Placenta Near Term

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, England, United Kingdom
Endocrinology (Impact Factor: 4.5). 01/2007; 147(12):5988-94. DOI: 10.1210/en.2006-0712
Source: PubMed


Preterm infants have low serum T4 and T3 levels, which may partly explain the immaturity of their tissues. Deiodinase enzymes are important in determining the bioavailability of thyroid hormones: deiodinases D1 and D2 convert T4 to T3, whereas deiodinase D3 inactivates T3 and produces rT3 from T4. In human and ovine fetuses, plasma T3 rises near term in association with the prepartum cortisol surge. This study investigated the developmental effects of cortisol and T3 on tissue deiodinases and plasma thyroid hormones in fetal sheep during late gestation. Plasma cortisol and T3 concentrations in utero were manipulated by exogenous hormone infusion and fetal adrenalectomy. Between 130 and 144 d of gestation (term 145+/-2 d), maturational increments in plasma cortisol and T3, and D1 (hepatic, renal, perirenal adipose tissue) and D3 (cerebral), and decrements in renal and placental D3 activities were abolished by fetal adrenalectomy. Between 125 and 130 d, iv cortisol infusion raised hepatic, renal, and perirenal adipose tissue D1 and reduced renal and placental D3 activities. Infusion with T3 alone increased hepatic D1 and decreased renal D3 activities. Therefore, in the sheep fetus, the prepartum cortisol surge induces tissue-specific changes in deiodinase activity that, by promoting production and suppressing clearance of T3, may be responsible for the rise in plasma T3 concentration near term. Some of the maturational effects of cortisol on deiodinase activity may be mediated by T3.

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    • "The activity of these enzymes has been studied in several organisms including human (Ishii et al., 1983), rat (Auf Dem Brinke et al., 1979), mouse (Harris et al., 1979), goat (Nicol et al., 1992), cow (Capuco et al., 1989; Cassar-Malek et al., 2007) and sheep (Polk et al., 1986; Wu et al., 1986). There are also several reports on the role of iodothyronine deiodinases in the developing fetus (Forhead et al., 2006; Harris et al., 1979; Sato et al., 1984). However, the relative levels of deiodinases in different tissues and their contribution to the establishment of a euthyroid state (proper production and concentration of T3 in blood) is not known (Kohrle and Gartner, 2009). "
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    ABSTRACT: Iodothyronine deiodinases I and II (DIO1 and DIO2) remove iodine from T4 to convert it to a more biologically active T3. The relative contribution of different tissue deiodinases to the establishment of a euthyroid state in sheep is not known. The objective of this study was to quantitate the amounts of transcription of DIO1 and DIO2 deiodinases in different ovine tissues. Using RT-qPCR, we found that DIO1 deiodinase is transcribed in skeletal muscle, kidney, and heart, more than thyroid, in diaphragm in quantities very similar to thyroid, and in liver, spleen, lung, and mammary gland lower than thyroid. We also found that the level of DIO2 transcription in all other tissues was lower than that in thyroid. In clinical settings, measurement of DIO1 and DIO2 expression in a given tissue may provide important clues on the intensity of selenium deficiency and its effects on the metabolism of thyroid hormones.
    Research in Veterinary Science 08/2013; 95(3). DOI:10.1016/j.rvsc.2013.07.010 · 1.41 Impact Factor
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    • "Such an EC-induced effect could be developmentally important as plasma T3 concentrations in the ovine fetus remain low for most of gestation because T4 is largely metabolized to biologically inactive rT3 and sulphated TH derivatives and placental enzymes inactivate T3 (Polk, 1995). It is only in the latter part of pregnancy when preferential deiodination of T4 to T3 occurs and this results in higher plasma T3 levels in the ovine fetus near term (Forhead et al., 2006; Polk, 1995). While studies of the effects of individual chemicals can be important mechanistically, environmental exposure is normally to a complex mixture of chemicals. "
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    ABSTRACT: Ewes were exposed to sewage sludge-fertilised pastures in a study designed investigate pre-conceptual and/or gestational exposure to environmental chemicals. The in-utero impact on fetal thyroid morphology and function at day 110 (of 145) of pregnancy was then determined. Pre-conceptual exposure increased the relative thyroid organ weights in male fetuses. The number of thyroid follicles in thyroids of fetuses after pre-conceptual or gestational exposure was reduced. This correlated with an increase in Ki67 positive cells. Pre-conceptual exposure to sewage sludge reduced small blood vessels in fetal thyroids. Thyroid tissues of exposed fetuses contained regions where mature angio-follicular units were reduced exhibiting decreased immunostaining for sodium-iodide symporter (NIS). Fetal plasma levels of fT3 and fT4 in exposed animals, however, were not different from controls suggesting compensatory changes in the thyroid gland to maintain homeostasis in exposed fetuses. The regional aberrations in thyroid morphology may impact on the post-natal life of the exposed offspring.
    Molecular and Cellular Endocrinology 01/2013; 367(1-2). DOI:10.1016/j.mce.2012.12.022 · 4.41 Impact Factor
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    • "Concentrations of T3, in particular, increase in the 2 h after birth of full-term pony foals in parallel with the rise in cortisol concentrations and are low in premature foals with hypocortisolaemia (Silver et al. 1991). Cortisol may, therefore, stimulate formation of T3 from thyroxine by activation of tissue deiodinases in the foal as occurs in the lamb during the prepartum period (Forhead et al. 2006). Cortisol may also be involved in inducing angiotensin converting enzyme (ACE) as pulmonary ACE activity increases during late Perinatal endocrine adaptations A. L. Fowden et al. gestation to peak at birth in line with the fetal cortisol concentrations in the foal (O'Connor et al. 2002). "
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    ABSTRACT: In adapting to life ex utero, the foal encounters a number of physiological challenges. It has to assume the nutritional, respiratory and excretory functions of the placenta and activate full regulatory control over its own internal environment for the first time. To achieve this, there must be structural and functional changes to a wide range of tissues including several endocrine glands. In most species, including the horse, these maturational changes begin in late gestation and continue into the first few days of neonatal life. Consequently, during this perinatal period, there are major changes in the sensitivity and/or set point of key endocrine axes, which alter the circulating hormone concentrations in the foal. In turn, these endocrine changes are responsible for many of the other physiological adaptations essential for neonatal survival. The perinatal alterations in the hypothalamic-pituitary-adrenal (HPA) axis are particularly important in these processes, although the sympatho-adrenal medullary axis and endocrine pancreas also have key roles in ensuring homeostasis during the multiple novel stimuli experienced at birth. Abnormalities in the perinatal endocrine profile caused by adverse conditions before or after birth may, therefore, lead to maladaptation or aid survival of the newborn foal depending on the specific circumstances. This review examines the perinatal changes in endocrinology in normal and compromised foals and the role of these endocrine changes in the physiological adaptations to extrauterine life with particular emphasis on the HPA axis, adreno-medullary catecholamines and the endocrine pancreas.
    Equine Veterinary Journal 02/2012; 44 Suppl 41(s41):130-9. DOI:10.1111/j.2042-3306.2011.00505.x · 2.37 Impact Factor
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