Molecular Human Reproduction, Vol. 8, No. 4, 318-325,
April 2002
© 2002 European Society of Human Reproduction and Embryology
Reproductive endocrinology |
Transforming growth factor-ß1 inhibits steroidogenesis in human trophoblast cells
Department of Biology, York University, 4700 Keele St, Toronto, Ontario, M3J 1P3, Canada
Abstract
Transforming growth factor-ß (TGF-ß) is an important regulator of placental development and function. In this study, we have investigated the effect of TGF-ß1 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-ß1 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-ß1 on P450 aromatase (P450arom) mRNA levels was determined by Northern blot analysis. TGF-ß1 significantly decreased progesterone production in both NPC and JEG-3 cells. The inhibitory effect of TGF-ß1 on progesterone production was reversed by addition of 22R-hydroxycholesterol, a membrane-permeable analogue of cholesterol, or pregnenolone. In JEG-3 cells, TGF-ß1 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-ß1 also suppressed aromatase mRNA levels. This study has demonstrated that TGF-ß1 inhibits progesterone and estradiol production by trophoblast cells, and that the sites of TGF-ß1 action on progesterone and estradiol production are likely to be cholesterol transport and P450arom respectively.
estradiol/JEG-3/NPC/progesterone/TGF-ß1
Notes
1 To whom correspondence should be addressed. E-mail: cpeng{at}yorku.ca
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