Sulfation is an important pathway of thyroid hormone metabolism that
facilitates the degradation of the hormone by the type I iodothyronine
deiodinase, but little is known about which human sulfotransferase
isoenzymes are involved. We have investigated the sulfation of the
prohormone T4, the active hormone T3, and the metabolites rT3 and
3,3'-diiodothyronine (3,3'-T2) by human liver and kidney cytosol as well
as by recombinant human SULT1A1 and SULT1A3, previously known as
phenol-preferring and monoamine-preferring phenol sulfotransferase,
respectively. In all cases, the substrate preference was 3,3'-T2 >> rT3 >
T3 > T4. The apparent Km values of 3,3'-T2 and T3 [at 50 micromol/L
3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9
micromol/L for liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol,
0.14 and 29.1 micromol/L for SULT1A1, and 33 and 112 micromol/L for
SULT1A3, respectively. The apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2)
was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for kidney cytosol,
0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3. The sulfation
of 3,3'-T2 was inhibited by the other iodothyronines in a
concentration-dependent manner. The inhibition profiles of the 3,3'-T2
sulfotransferase activities of liver and kidney cytosol obtained by
addition of 10 micromol/L of the various analogs were better correlated
with the inhibition profile of SULT1A1 than with that of SULT1A3. These
results indicate similar substrate specificities for iodothyronine
sulfation by native human liver and kidney sulfotransferases and
recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the
highest affinity for both iodothyronines and PAPS, but it remains to be
established whether it is the prominent isoenzyme for sulfation of thyroid
hormone in human liver and kidney