3 research outputs found
Characterization of iodothyronine sulfatase activities in human and rat liver and placenta
In conditions associated with high serum iodothyronine sulfate
concentrations, e.g. during fetal development, desulfation of these
conjugates may be important in the regulation of thyroid hormone
homeostasis. However, little is known about which sulfatases are involved
in this process. Therefore, we investigated the hydrolysis of
iodothyronine sulfates by homogenates of V79 cells expressing the human
arylsulfatases A (ARSA), B (ARSB), or C (ARSC; steroid sulfatase), as well
as tissue fractions of human and rat liver and placenta. We found that
only the microsomal fraction from liver and placenta hydrolyzed
iodothyronine sulfates. Among the recombinant enzymes only the endoplasmic
reticulum-associated ARSC showed activity toward iodothyronine sulfates;
the soluble lysosomal ARSA and ARSB were inactive. Recombinant ARSC as
well as human placenta microsomes hydrolyzed iodothyronine sulfates with a
substrate preference for 3,3'-diiodothyronine sulfate (3,3'-T(2)S)
approximately T(3) sulfate (T(3)S) >> rT(3)S approximately T(4)S, whereas
human and rat liver microsomes showed a preference for 3,3'-T(2)S > T(3)S
>> rT(3)S approximately T(4)S. ARSC and the tissue microsomal sulfatases
were all characterized by high apparent K(m) values (>50 microM) for
3,3'-T(2)S and T(3)S. Iodothyronine sulfatase activity determined using
3,3'-T(2)S as a substrate was much higher in human liver microsomes than
in human placenta microsomes, although ARSC is expressed at higher levels
in human placenta than in human liver. The ratio of estrone sulfate to
T(2)S hydrolysis in human liver microsomes (0.2) differed largely from
that in ARSC homogenate (80) and human placenta microsomes (150). These
results suggest that ARSC accounts for the relatively low iodothyronine
sulfatase activity of human placenta, and that additional arylsulfatase(s)
contributes to the high iodothyronine sulfatase activity in human liver.
Further research is needed to identify these iodothyronine sulfatases, and
to study the physiological importance of the reversible sulfation of
iodothyronines in thyroid hormone metabolism
Characterization of human iodothyronine sulfotransferases
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
Sulfation of thyroid hormone by estrogen sulfotransferase
Sulfation is one of the pathways by which thyroid hormone is inactivated.
Iodothyronine sulfate concentrations are very high in human fetal blood
and amniotic fluid, suggesting important production of these conjugates in
utero. Human estrogen sulfotransferase (SULT1E1) is expressed among other
tissues in the uterus. Here we demonstrate for the first time that SULT1E1
catalyzes the facile sulfation of the prohormone T4, the active hormone T3
and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) with preference
for rT3 approximately 3,3'-T2 > T3 approximately T4. Thus, a single enzyme
is capable of sulfating two such different hormones as the female sex
hormone and thyroid hormone. The potential role of SULT1E1 in fetal
thyroid hormone metabolism needs to be considered