Effects of DHA-S on placental 3 beta-hydroxysteroid dehydrogenase activity, progesterone and 20 alpha-dihydroprogesterone concentrations in placenta and serum.
To study the effects of dehydroepiandrosterone sulfate (DHA-S) on placental steroid metabolism and maternal steroidal profiles at term, the following in vivo and in vitro experiments were performed. Two hundred mg of DHA-S was given to five pregnant women 30 minutes prior to delivery. After delivery, the placenta was collected and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and sulfatase activity was determined by measuring the rate of conversion of pregnenolone to progesterone and DHA-S to DHA. The amount of C21-delta 4-steroid in the placental tissue was measured by gas chromatography mass spectrometry (GC-MS) and compared with the control groups. The maternal serum concentration of several steroids was also measured by GC-MS before and after the administration of DHA-S. 3 beta-HSD activity in the placentae from the mothers who received DHA-S before delivery was significantly lower than in the controls. On the other hand, no significant change was observed in the activity of sulfatase. The serum concentration of progesterone (P) and 20 alpha-dihydro-P (20-P) before DHA-S loading decreased following the administration whereas estradiol (E), DHA, and androstenedione (A) levels increased. To study the direct effect of DHA-S and its related steroids on placental 3 beta-HSD activity, placental tissue samples were incubated with pregnenolone in vitro. Several other steroids were added simultaneously into the medium. It was observed that placental 3 beta-HSD activity was directly inhibited by DHA-S. These results indicate that DHA-S inhibits 3 beta-HSD activity in the placenta and subsequently causes a reduction in P and 20-P.
Watanabe
H
H
Department of Obstetrics and Gynecology, School of Medicine, Showa University Tokyo, Japan.
Hirato
K
K
Hashino
M
M
Kosaki
T
T
Kimura
T
T
Nakayama
T
T
Yanaihara
T
T
D004092:20-alpha-Dihydroprogesterone / Q000096:biosynthesis*; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000735:Androstenedione / Q000097:blood; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate; D004958:Estradiol / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000031:analogs & derivatives* / Q000096:biosynthesis*
D004092:20-alpha-Dihydroprogesterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D015096:3-Hydroxysteroid Dehydrogenases