Steroid sulfohydrolase activity in human chorion. I. Interactions of other steroids with estrone sulfate as substrate.
Human chorion contains steroid sulfohydrolase activity and synthesizes free estrogens from estrone sulfate (E1S). We hypothesized that the free estrogen thus formed may influence the contractility of the adjacent myometrium in late pregnancy. In this study we measured the abilities of various steroids and steroid conjugates to influence the hydrolysis of E1S by the 105,000 x g pellet of chorion tissue obtained from women after spontaneous onset of labor and vaginal delivery and from women delivered by cesarean section before labor onset. No differences were found in tissues obtained before or after the onset of labor. None of the steroids increased the rate of hydrolysis. Several unconjugated steroids caused significant inhibition, but only at concentrations well beyond physiological ranges in maternal or fetal blood. However, conjugated steroids had marked inhibitory effects at circulating concentrations. At equimolar concentrations with the E1S substrate, the sulfoconjugates of dehydroepiandrosterone, pregnenolone, and cholesterol caused 27 +/- 1% (+/- SE), 64 +/- 1%, and 40 +/- 1% inhibition, respectively. These results were confirmed using a tissue explant system. Using enzyme inhibition kinetic analysis, we determined that the inhibition by dehydroepiandrosterone sulfate was non-competitive, with Ki = 8.7 +/- 1.7 mumol/L. The inhibition by pregnenolone sulfate was competitive, with Ki = 1.6 +/- 0.4 mumol/L, and that by cholesterol sulfate was primarily noncompetitive, with Ki = 7.4 +/- 1.2 mumol/L. We conclude that there is significant interaction among sulfurylated steroids that may influence local free estrogen synthesis within human chorion. This interaction may affect the contractility of the late pregnancy myometrium.
Chibbar
R
R
Department of Obstetrics and Gynecology, University of Western Ontario, St. Joseph's Health Centre, London, Canada.
Mitchell
B F
BF
D002823:Chorion / Q000201:enzymology*; D046508:Culture Techniques; D004347:Drug Interactions; D004970:Estrone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D011247:Pregnancy; D013256:Steroids / Q000494:pharmacology / Q000502:physiology*; D043266:Steryl-Sulfatase; D013429:Sulfatases / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D013256:Steroids; D004970:Estrone; D013429:Sulfatases; D043266:Steryl-Sulfatase; C017296:estrone sulfate