Conversion of Thyroxine to Triiodothyronine and Reverse Triiodothyronine in Human Placenta and Fetal Membranes

Banovac, K; Bzik, L; Tišlarić, Dubravka; Sekso, M

doi:10.1159/000179128

Cited by 40 publications

(9 citation statements)

References 7 publications

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“…The added T4 concentration in assay C, 1 nM, was much greater than that contributed by the T4 content of cells cultured in either type of serum: 125±25 pM from cells in normal calf serum and 26±6 pM from cells in THDCS, as monitored by tracer T4 added to parallel wells. 2 Thus, all three assays showed a near doubling of 5'-deiodination after 48 h deprivation ofthyroid hormone. The increase 2.…”

Section: Methodsmentioning

confidence: 79%

“…The chorion-decidual membrane was then minced and submitted to digestion in HBSS with 2 Cells liberated between 30 and 90 min were passed through a 149-gm nylon mesh and collected. Cell viability, assessed by trypan blue exclusion, was 82-94%.…”

Section: Methodsmentioning

confidence: 99%

“…Human and rat placenta have an iodothyronine 5'-deiodinating pathway that is thiol dependent, largely localized to particulate subcellular fractions, and insensitive to inhibition by 6-n-propylthiouracil (PTU)' (1,2). It has an apparent Michaelis constant (Ki) for L-thyroxine (T4) of 2-3 nM, and T4 is a better substrate than 3,3',5'-L-triiodothyronine (rT3), as judged by a higher ratio of apparent maximum reaction velocity (Vmax) to Km for T4.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of thyroxine 5'-deiodination in cultured human placental cells. Regulation by iodothyronines.

Hidal¹,

Kaplan²

1985

J. Clin. Invest.

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Section: Methodsmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characteristics of thyroxine 5'-deiodination in cultured human placental cells. Regulation by iodothyronines.

Hidal¹,

Kaplan²

1985

J. Clin. Invest.

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“…It is also shown that T4 is converted to 3,3',5'-tri-iodothyronine (reverse T3) in the brain (Kaplan and Yaskoski 1980), liver (Cavaliers et al 1977), kidney (Yoshida et al 1982) and leucocytes (Woeber 1978). Recently, it has been reported that T4 is metabolized in the placenta (Banovac et al 1980; Roti et al 1981). In the present paper, we describe the T4 monodeiodination to reverse T3 in vitro in the human placental homogenate and subcellular fractions obtained from the placentas at normal delivery.…”

mentioning

confidence: 99%

Monodeiodination of thyroxine to 3,3',5'-triiodothyronine in the human placenta.

Suzuki

Yoshida

Sato

et al. 1983

Tohoku J. Exp. Med.

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We studied the characteristics of monodeiodination of thyroxine to T3 and reverse T3 in the human placenta which was obtained at normal delivery. The placentas were homogenized in cold sucrose Tris-HC1 buffer, pH 7.5. The microsomal fraction was incubated at 37°C in the air for 1 hr with 2 yg of T4 in the presence of 0.05 M DTT. The T3 and reverse T3 generated in the reaction mixture were extracted into cold ethanol and measured by RIA. Among the usual subcellular fractions of the placental homogenate, microsomas were most potent in deiodinating T4 to reverse T3, 17.9 ng/mg protein/ ,ug T4/60 min. In microsome, production of reverse T3 from T4 was dependent upon protein concentration, incubation temperature, incubation time, pH and T4 concentration, and unstable to prior heating of the microsomal fraction. The production of T3 from T4 was negligible in the present system. Degradation of T3 in the human placenta was rapid. Although addition of anti-T3 antibody to the reaction mixture suppressed the degradation of T3, it had no effect on the net production of T3, suggesting that the obtained net T3 production rate had not been influenced by its degradation. Degradation of reverse T3 was negligible. These results indicate that the human placenta actively deiodinates T4 to reverse T3 enzymatically. This enzyme system might have some influence on the transplacental passage of thyroid hormone from the mother to the fetus.

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“…The iodothyronine markers were detected at a wavelength of 254 nm and were used as reference points for 1251 radioactivity eluting from the column. Table I shows the retention times for ['25Iliodide and stable 3'-TI, 3,3'-T2, 3',5'-T2, 3,5-T2, T3, and T4. HPLC eluate fractions were collected every 0.6 min and counted in a gamma counter.…”

Section: Methodsmentioning

confidence: 99%

Inner-ring deiodination of 3,5,3'-triiodothyronine in the in situ perfused guinea pig placenta.

Castro¹,

Braverman²,

Alex³

et al. 1985

J. Clin. Invest.

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IntroductionBroken cell preparations of rat and human placentas contain an inner (tyrosyl)-ring iodothyronine deiodinase enzyme with greatest activity when the substrate is 3,5,3'-triiodothyronine (T3). This report describes the deiodination of T3 in the intact placenta and the effect of sodium iopanoate (IA) and propylthiouracil (PTU) on T3 deiodination. Under nembutal anesthesia, the placenta of60-65-d-old pregnant guinea pigs was surgically exposed, a single umbilical artery and the umbilical vein were cannulated, and the fetus was removed. In a temperature-controlled chamber (37°C), the fetal side of the placenta was perfused through the umbilical artery at a rate of 1 ml/min with 3% bovine serum albumin Krebs-Henseleit buffer containing 0.14 nM outer ring labeled 1'"IJT3. Placenta effluent fractions were collected at timed intervals from the umbilical vein canulla throughout a 120-min perfusion period. The contents of the perfusion buffer and the various effluent fractions were analyzed for their iodothyronine content by high pressure liquid chromatography. In five experiments, the percent composition of '25I-labeled iodothyronines in the perfusion buffer and placenta effluent was 95.3±1.0 (mean±SE) and 70.2±2.1 for T3 (P < 0.01), 2.5±0.7 and 20.1±1.8 for 3,3'-T2 (P < 0.01), and 0 and 8.2±0.9 for 3'-Ti. The placenta receives a large percentage of the fetal cardiac output (1), and, as we and others have reported (2-7), contains enzymes that deiodinate thyroid hormones. These observations support the possibility that the placenta is an important site for fetal thyroid hormone metabolism. Deiodination of the iodothyronines can occur in the phenolic (5' or outer) or in the tyrosyl (5 or inner) rings. These deiodinative pathways play a major role in the metabolism of thyroxine (T4),' generating the metabolically active iodothyronine, 3,5,3'-triiodothyronine (T3), and the metabolically inactive iodothyronine, 3,3',5'-triiodothyronine (rT3). Deiodination is also the principal pathway for the metabolism of T3, which results in the formation of the inactive diiodothyronines, 3,3'-T2 and 3,5-T2, as well as the inactive monoiodothyronines, 3'-T, and 3-T1. Thus, placental deiodination is potentially an important mechanism for the modulation of fetal thyroid hormone action. While detailed studies of deiodination have been performed in placenta homogenates and subcellular fractions (6,8), there is little information on iodothyronine deiodination in the intact placenta (9).In this study, we discovered the metabolic fate of T3 when perfused through the fetal side ofthe guinea pig placenta in situ. Since previous studies employing placenta homogenates have shown an inhibitory effect ofpropylthiouracil (PTU) and sodium iopanoate (IA) on T4 deiodination (8), the effect of these drugs on T3 metabolism in the intact placenta was evaluated.

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Conversion of Thyroxine to Triiodothyronine and Reverse Triiodothyronine in Human Placenta and Fetal Membranes

Cited by 40 publications

References 7 publications

Characteristics of thyroxine 5'-deiodination in cultured human placental cells. Regulation by iodothyronines.

Characteristics of thyroxine 5'-deiodination in cultured human placental cells. Regulation by iodothyronines.

Monodeiodination of thyroxine to 3,3',5'-triiodothyronine in the human placenta.

Inner-ring deiodination of 3,5,3'-triiodothyronine in the in situ perfused guinea pig placenta.

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