Iodothyronine sulfotransferase activity in rat uterus during gestation.
In developing mammals, we and others demonstrated that sulfation is an important pathway in the metabolism of thyroid hormone, and there is significant fetal-maternal transfer of sulfated iodothyronine. In the present study, we characterized a novel iodothyronine sulfotransferase (IST) in pregnant rat uterus. (125)I-labeled 3,3'-diiodothyronine (T(2)), T(3), rT(3), and T(4) were used as substrates with unlabeled 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as the sulfate donor. Sulfated iodothyronine products were separated by Sephadex LH-20 column and further identified on reverse phase HPLC. We measured IST activity in pregnant rat uterus by incubating 1 microM substrate, 50 microM PAPS, and 50 microg cytosol protein, pH 7.2, 30 min at 37 degrees C. The results show that the substrate preference of the uterine IST activity is: T(2 )> rT(3 )> T(3)> T(4); the pH optimum is 6.0 for T(2). The K(m) and V:(max) (for gestational day 21 uterus) for T(2) are 0.62 microM and 3466 pmol/mg protein/h, respectively; for PAPS the values are 2.6 microM and 1523 pmol/mg protein/h, respectively. During pregnancy, the total activities exhibit a U-shaped curve with minimum activity at day 13 of gestation; while a thermostable activity increases significantly near term. In summary, there is significant uterine IST that varies during pregnancy. The role of this uterine sulfotransferase activities in regulating the bioavailability of thyroid hormone in the developing fetus remains to be elucidated.
Wu
S Y
SY
Nuclear Medicine and Medicine Services, Department of Veterans' Affairs Medical Center, Long Beach, CA 90822, USA.
Huang
W S
WS
Fisher
D A
DA
Florsheim
W H
WH
St Germain
D L
DL
Galton
V A
VA
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D005260:Female; D005865:Gestational Age; D006358:Hot Temperature; D007527:Isoenzymes / Q000032:analysis* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011489:Protein Denaturation; D051381:Rats; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000032:analysis* / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D014599:Uterus / Q000201:enzymology*
D007527:Isoenzymes; D014284:Triiodothyronine; D015238:Sulfotransferases; C109377:iodothyronine sulfotransferase; D013974:Thyroxine