Origin of deoxycorticosterone and deoxycorticosterone sulfate in human pregnancy: absence of steroid 21-sulfatase activity in sulfatase-deficient placenta.
The activity of steroid 21-sulfatase, the enzyme that catalyzes the hydrolysis of deoxycorticosterone sulfate (DOC-SO4) is demonstrable in human placenta. Thus, it is possible that this placental enzyme, by way of the hydrolysis of either DOC-SO4 or 21-hydroxypregnenolone mono- or di-sulfate of fetal origin, may be important in the biosynthesis of DOC, which is present in the plasma of pregnant women in high concentration. To investigate this issue further, we evaluated steroid 21-sulfatase activity in microsomal preparations of a sulfatase-deficient placenta. Immediately after delivery, at term, of a living male fetus with sulfatase deficiency, a microsome-enriched fraction of placental tissue was prepared; sulfatase activity was evaluated by use of three substrates, viz. dehydroisoandrosterone sulfate (DS), estrone sulfate (E1-SO4), and DOC-SO4, in various concentrations. Similar incubations were conducted with aliquots of a microsome-enriched fraction prepared from placental tissue of a normal fetus that was delivered, at term, within minutes of the time of delivery of the infant with sulfatase deficiency. In microsomal fractions from the normal placenta, each of the steroid sulfates was hydrolyzed. In the absence of microsomes, and in the presence of microsomal fractions from the sulfatase-deficient placenta, the hydrolysis of DOC-SO4 and DS was not detected. Moreover, in microsomes prepared from the sulfatase-deficient placenta, E1-SO4 was hydrolyzed at a rate that was only 10% of that in incubations with microsomal preparations of the normal placenta. We conclude that with sulfatase deficiency, the placenta is deficient not only in sulfatase activity for steroid-3-sulfates but for steroid 21-sulfates, e.g. DOC-SO4, as well.
Guerami
A
A
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical School, Dallas 75235.
Varner
M W
MW
Shackleton
C H
CH
MacDonald
P C
PC
Casey
M L
ML
D006907:17-alpha-Hydroxypregnenolone / Q000032:analysis; D000328:Adult; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000032:analysis / Q000201:enzymology*; D011247:Pregnancy; D011374:Progesterone / Q000032:analysis; D013379:Substrate Specificity; D013429:Sulfatases / Q000172:deficiency*
C032268:deoxycorticosterone sulfate; D006907:17-alpha-Hydroxypregnenolone; D003900:Desoxycorticosterone; D011374:Progesterone; C052374:21-hydroxypregnenolone; D013429:Sulfatases; C038087:steroid 21-sulfatase