Identification of 3,3'-T2S as a fetal thyroid hormone derivative in maternal urine in sheep

Wu, Sing-Yung; Polk, Daniel H.; Fisher, Delbert A.; Huang, Wen‐Sheng; Reviczky, A.; Chen, Wei-Lian

doi:10.1152/ajpendo.1995.268.1.e33

Cited by 16 publications

(28 citation statements)

References 11 publications

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“…Similarly to fetal T 3 infusion, the most abundant metabolite found in maternal urine following radioactive T 4 infusion is T 2 S ( Table 2). The T 4 infusion study confirms previous data in ovine fetuses (2,4,6) indicating that the production of active thyroid hormone (T 3 ) is less than production of inactive products (1.8 versus 3.1% dose/L, respectively in h 1 and 1.9 versus 8.9% dose/L, respectively in h 4, Table 1). It is also interesting that free iodide comprises 14.5-16.8% dose/L generated in the first 3 h and this far exceeds the identified metabolites (4.9 -6.5% dose/L in total).…”

Section: Discussionsupporting

confidence: 88%

“…After T 3 infusion, however, T 2 S specific activity in both serum and urine reached a peak early, around h 2, whereas the specific T 2 S activity continued to increase up to 24 h after T 4 infusion, even though activity was much lower than that after T 3 infusion. These data suggest that T 2 S is formed mainly in the fetal compartment and then transferred to the maternal side and finally excreted into maternal urine (4,6). The rate of T 2 S formed from T 3 is significantly higher than that from T 4 ( Table 4).…”

Section: Thyroid Hormone Transfer In Sheepmentioning

confidence: 84%

“…Urine and serum samples were extracted with two volumes of 95% ethanol and subsequently lyophilized. The dried extracts were dissolved in 1 mL of H 2 O and purified using an LH-20 column as previously described (6). After application to an HPLC -Bondapak C 18 column (Waters, Milford, MA), the extracts were eluted isocratically with a mixture of acetonitrile and 0.02M ammonium acetate, pH 4.0 (22:78 vol/vol) at a flow rate of 2 mL/min.…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, when a supraphysiological dose of T 3 , about 200-fold the fetal T 3 PR, was infused into fetuses, both T 2 S and T 3 S were found in maternal urine (6). To exclude the possibility that the observed fetal-to-maternal transfer of metabolites could be a pharmacological dose effect, the present study was conducted to quantify the radioactivities and identify the metabolites in fetal serum and maternal serum and urine following fetal infusion of 125 I-T 4 contrasted with results after infusion of 125 I-T 3 .…”

mentioning

confidence: 93%

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Fetal-to-Maternal Transfer of Thyroid Hormone Metabolites in Late Gestation in Sheep

Polk

Huang

et al. 2006

Pediatr Res

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3,3=-diiodothyronine sulfate (T 2 S) derived from T 3 of fetal origin is transferred to the maternal circulation and contributes significantly to the maternal urinary pool. The present study quantitatively assesses the fetal to maternal transfer of T 4 metabolites compared with those of T 3 . Labeled T 4 or T 3 was infused intravenously to four singleton fetuses in utero in each group at gestational age 138 Ϯ 3 d. Maternal and fetal serum and maternal urine samples were collected hourly for 4 h and at 24 h (serum) or in pooled 4 -24 h samples (urine). Radioactive metabolites were identified by HPLC and by specific antibody in serum and urine extracts and expressed as percentage infusion dose per liter. The results demonstrate a rapid clearance of labeled T 3 from fetal serum (disappearance T 1/2 of 0.7 h versus 2.4 h for T 4 in the first 4 h). The metabolites found in fetal serum after labeled T 3 infusion were T 2 S Ͼ T 3 Ͼ T 3 S; in maternal urine, T 2 S Ͼ unconjugated iodothyronines (UI) Ͼ T 3 S Ͼ unknown metabolite (UM). After labeled T 4 infusion, the metabolites in fetal serum were rT 3 Ͼ T 3 Ͼ T 2 S Ͼ T 4 S in the first 4 h, and rT 3 ϭ T 3 ϭ T 4 S ϭ T 2 S Ͼ T 3 S at 24 h; in maternal urine we found T 2 S Ͼ UM Ͼ UI Ͼ T 4 S Ͼ T 3 S in the first 4 h and UM Ͼ T 2 S Ͼ UI in 4 -24 h pooled sample. In conclusion, the conversion of T 3 to T 2 S followed by fetal to maternal transfer of T 2 S and other iodothyronines appears to contribute importantly to maintaining low fetal T 3 levels in late gestation. (Pediatr Res 59: 102-106, 2006) K inetic studies in fetal sheep in late gestation (Ͼ135 d of gestational age; term, 150 d) showed that mean fetal T 4 CR and PR are significantly higher than the corresponding values in adult sheep (1). The ratio of mean PR of rT 3 to T 4 is similar in fetal and adult sheep, whereas the PR ratio of T 3 to T 4 in fetal sheep is much lower than that in adult sheep. These data in the ovine fetus indicate that the prevailing low serum T 3 concentration is due both to increased CR and decreased PR, whereas the elevated serum rT 3 levels are due to decreased CR and increased PR. We and others showed that sulfated iodothyronines, including T 4 S, T 3 S, rT 3 S, and 3,3=-T 2 S are major T 4 metabolites in ovine fetuses (2,3). The PR of T 4 S, T 3 S, rT 3 S, and rT 3 significantly exceed the PR of T 3 .Thus, peripheral thyroid hormone metabolism in the ovine fetus, in contrast to the adult, is shunted to inactivation rather than production of active hormone.In a recent study, we showed that a significant amount of 3,3=-diiodothyronine (T 2 ), the inner-ring deiodinated metabolite of fetal T 3 , is found in maternal urine as sulfated T 2 when 125 I-T 3 is infused in venously catheterized fetuses (4,5). In contrast, when a supraphysiological dose of T 3 , about 200-fold the fetal T 3 PR, was infused into fetuses, both T 2 S and T 3 S were found in maternal urine (6). To exclude the possibility that the observed fetal-to-maternal transfer of metabolites could be a pharmacological dose...

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Section: Discussionsupporting

confidence: 88%

Section: Thyroid Hormone Transfer In Sheepmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 93%

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Fetal-to-Maternal Transfer of Thyroid Hormone Metabolites in Late Gestation in Sheep

Polk

Huang

et al. 2006

Pediatr Res

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“…Five to 10 mL cord or maternal serum were extracted with 2 vol 95% ethanol and subsequently lyophilized. The dried extracts were dissolved in H 2 O and purified with an LH-20 column, as previously described (1,6). Radioactive or nonradioactive T 2 S-supplemented serum extracts from nonpregnant women were used to identify the T 2 S peak on HPLC.…”

mentioning

confidence: 99%

Compound W, a 3,3′-Diiodothyronine Sulfate Cross-Reactive Substance in Serum from Pregnant Women—A Potential Marker for Fetal Thyroid Function

Huang

et al. 2007

Pediatr Res

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Compound W, a 3,3=-diiodothyronine sulfate (T 2 S) cross-reactive material in maternal serum, was found to be useful as a marker for fetal hypothyroidism. In the present report, we explored its biochemical properties and studied its concentrations in cord and in maternal serum obtained from various gestational periods and at term from different continents. Mean W concentrations, expressed as nmol/L T 2 S-equivalent, in maternal serum during gestation showed a moderate increase at 20 -26 wk (1.57 nmol/L) and an accelerated increase to 34 -40 wk (3.59 nmol/L). The mean serum level was relatively low in nonpregnant women (0.17 nmol/L). Compound W levels in cord and maternal serum at term were not significantly different among samples obtained from Taiwan compared with samples from the United States. The mean cord serum "corrected" (by hot acid digestion) concentrations of W were significantly higher than maternal serum concentrations at birth and were also higher in venous than in paired arterial samples, suggesting that the placenta may play a role in its production. We compared a total of 45 iodothyronine analogs by antibody, gel filtration, and HPLC chromatographic studies and found only one compound, N,N-dimethyl- E mploying a sensitive RIA for T 2 S, we found high concentrations in fetal and pregnant serum in humans (1). We further identified that this T 2 S-cross-reactive material is not authentic T 2 S and does not co-chromatograph with synthetic T 2 S on HPLC. Thus, the name Compound W was coined to represent this material in fetal and maternal serum (1). Levels increased with the progression of pregnancy and rapidly peaked before parturition. At delivery, a 20-fold increase in "T 2 S" was found compared with nonpregnant women and returned to baseline within 7-10 d. Serial measurements of serum W in pregnant women have been found to be useful as a noninvasive technique for the diagnosis of fetal hypothyroidism (2,3).The present study was undertaken to determine the normal distribution of elevated Compound W levels in different stages of pregnancy as well as from various geographic areas and correlate between paired maternal and cord blood samples, and to explore its origin and chemical structure. MATERIALS AND METHODS T 2 S RIA. 3,3=-T 2 S and [125 I]T 2 S were prepared by the method of Eelkman-Rooda and co-workers (4,5). T 2 S was further purified and quantitatively recovered by reverse-phase HPLC with a preparative column, as described previously (1,2,4).The T 2 S RIA procedure was a modification of the RIA described previously (1,2). Serum samples (0.2-1.0 mL) were extracted with 2 vol 95% ethanol (final concentration, 63%) before assay. Preliminary experiments showed that the extraction efficiency of T 2 S in serum exceeded 96%. Final T 2 S concentrations were not corrected for recovery. The lower limit of detection of the assay was 3.3 fmol (2 pg), or 33.1 pmol/L in a 300 L ethanol extract of serum. Intra-assay variations were 1.9 -9.1% and interassay variations were 6.0 -19.5%, depending on ...

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Fetal and Neonatal Thyroid Physiology

Polk¹,

Fisher²

2011

Fetal and Neonatal Physiology

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Identification of 3,3'-T2S as a fetal thyroid hormone derivative in maternal urine in sheep

Cited by 16 publications

References 11 publications

Fetal-to-Maternal Transfer of Thyroid Hormone Metabolites in Late Gestation in Sheep

Fetal-to-Maternal Transfer of Thyroid Hormone Metabolites in Late Gestation in Sheep

Compound W, a 3,3′-Diiodothyronine Sulfate Cross-Reactive Substance in Serum from Pregnant Women—A Potential Marker for Fetal Thyroid Function

Fetal and Neonatal Thyroid Physiology

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