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
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. L Jones, C. Stoikos, J. K Findlay, and L. A Salamonsen TGF-{beta} superfamily expression and actions in the endometrium and placenta. Reproduction, August 1, 2006; 132(2): 217 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-r. Zhao, W. Qiu, Y.-x. Li, Z.-b. Zhang, D. Li, and Y.-l. Wang Dual effect of transforming growth factor {beta}1 on cell adhesion and invasion in human placenta trophoblast cells. Reproduction, August 1, 2006; 132(2): 333 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Dimitriadis, C.A. White, R.L. Jones, and L.A. Salamonsen Cytokines, chemokines and growth factors in endometrium related to implantation Hum. Reprod. Update, November 1, 2005; 11(6): 613 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Munir, G. Xu, Y. Wu, B. Yang, P. K. Lala, and C. Peng Nodal and ALK7 Inhibit Proliferation and Induce Apoptosis in Human Trophoblast Cells J. Biol. Chem., July 23, 2004; 279(30): 31277 - 31286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Roberts, S. Hu, Q. Qiu, P. C.K. Leung, I. Caniggia, A. Gruslin, B. Tsang, and C. Peng Identification of Novel Isoforms of Activin Receptor-Like Kinase 7 (ALK7) Generated by Alternative Splicing and Expression of ALK7 and Its Ligand, Nodal, in Human Placenta Biol Reprod, May 1, 2003; 68(5): 1719 - 1726. [Abstract] [Full Text] [PDF]
|
|