Transforming growth factor-beta1 inhibits steroidogenesis in human trophoblast cells.
Transforming growth factor-beta (TGF-beta) is an important regulator of placental development and function. In this study, we have investigated the effect of TGF-beta1 on steroidogenesis, as well as its sites of action in the steroidogenic pathway by using a choriocarcinoma cell line, JEG-3, and a normal trophoblast cell line (NPC). The effect of TGF-beta1 on progesterone and estradiol production was evaluated in the absence or presence of a membrane-permeable analogue of cholesterol and some intermediate substrates of steroidogenic enzymes. The effect of TGF-beta1 on P450 aromatase (P450arom) mRNA levels was determined by Northern blot analysis. TGF-beta1 significantly decreased progesterone production in both NPC and JEG-3 cells. The inhibitory effect of TGF-beta1 on progesterone production was reversed by addition of 22R-hydroxycholesterol, a membrane-permeable analogue of cholesterol, or pregnenolone. In JEG-3 cells, TGF-beta1 also inhibited estradiol production when androstenedione, but not estrone, was added to the culture. Estradiol production was too low to be detected in NPC cells. Treatment with TGF-beta1 also suppressed aromatase mRNA levels. This study has demonstrated that TGF-beta1 inhibits progesterone and estradiol production by trophoblast cells, and that the sites of TGF-beta1 action on progesterone and estradiol production are likely to be cholesterol transport and P450arom respectively.
Luo
Shuang
S
Department of Biology, York University, 4700 Keele St, Toronto, Ontario, M3J 1P3, Canada.
Yu
Hui
H
Wu
Dongning
D
Peng
Chun
C
D028341:Activins / Q000378:metabolism; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D004958:Estradiol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D038681:Follistatin; D006801:Humans; D011374:Progesterone / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014327:Trophoblasts / Q000378:metabolism*
D038681:Follistatin; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D028341:Activins; D011374:Progesterone; D004958:Estradiol; D001141:Aromatase