|
Originally published In Press as doi:10.1074/jbc.M409486200 on December 21, 2004
J. Biol. Chem., Vol. 280, Issue 10, 9135-9148, March 11, 2005
Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad*
Youngkyu Park ,
Evelyn T. Maizels,
Zachary J. Feiger,
Hena Alam,
Carl A. Peters,
Teresa K. Woodruff ,
Terry G. Unterman¶,
Eun Jig Lee||,
J. Larry Jameson||, and
Mary Hunzicker-Dunn**
From the
Departments of Cell and Molecular Biology and ||Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, the Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, and the ¶Department of Medicine, University of Illinois College of Medicine and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612
Ovarian follicles undergo exponential growth in response to follicle-stimulating hormone (FSH), largely as a result of the proliferation of granulosa cells (GCs). In vitro under serum-free conditions, rat GCs differentiate in response to FSH but do not proliferate unless activin is also present. In the presence of FSH plus activin, GCs exhibit enhanced expression of cyclin D2 as well as inhibin- , aromatase, steroidogenic factor-1 (SF-1), cholesterol side chain (SCC), and epiregulin. In this report we sought to identify the signaling pathways by which FSH and activin promote GC proliferation and differentiation. Our results show that these responses are associated with prolonged Akt phosphorylation relative to time-matched controls and are dependent on phosphatidylinositol 3-kinase (PI 3-kinase) and Smad2/3 signaling, based on the ability of the PI 3-kinase inhibitor LY294002 or infection with adenoviral dominant negative Smad3 (DN-Smad3) mutant to attenuate induction of cyclin D2, inhibin-, aromatase, SCC, SF-1, and epiregulin. The DN-Smad3 mutant also abolished prolonged Akt phosphorylation stimulated by FSH plus activin 24 h post-treatment. Infection with the adenoviral constitutively active forkhead box-containing protein, O subfamily (FOXO)1 mutant suppressed induction of cyclin D2, aromatase, inhibin-, SF-1, and epiregulin. Transient transfections of GCs with constitutively active FOXO1 mutant also suppressed cyclin D2, inhibin-, and epiregulin promoter-reporter activities. Chromatin immunoprecipitation results demonstrate in vivo the association of FOXO1 with the cyclin D2 promoter in untreated GCs and release of FOXO1 from the cyclin D2 promoter upon addition of FSH plus activin. These results suggest that proliferation and differentiation of GCs in response to FSH plus activin requires both removal of FOXO1-dependent repression and positive signaling from Smad2/3.
Received for publication, August 18, 2004
, and in revised form, December 15, 2004.
* This work was funded by National Institutes of Health Grants P01 HD21921 (to M. H.-D. and J. L. J.), R01 HD044464 (to T. K. W.), and R01 DK41430 (to T. G. U.) and by the Department of Veterans Affairs Merit Review Program (to T. G. U.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
** To whom correspondence should be addressed: Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Tel.: 312-503-8940; Fax: 312-503-0566; E-mail: mhd{at}Northwestern.edu.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Xia and A. L Schneyer
The biology of activin: recent advances in structure, regulation and function
J. Endocrinol.,
July 1, 2009;
202(1):
1 - 12.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Liu, M. D. Rudd, I. Hernandez-Gonzalez, I. Gonzalez-Robayna, H.-Y. Fan, A. J. Zeleznik, and J. S. Richards
FSH and FOXO1 Regulate Genes in the Sterol/Steroid and Lipid Biosynthetic Pathways in Granulosa Cells
Mol. Endocrinol.,
May 1, 2009;
23(5):
649 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-Y. Yu, S. H. Reynolds, S. D. Hatfield, H. R. Shcherbata, K. A. Fischer, E. J. Ward, D. Long, Y. Ding, and H. Ruohola-Baker
Dicer-1-dependent Dacapo suppression acts downstream of Insulin receptor in regulating cell division of Drosophila germline stem cells
Development,
May 1, 2009;
136(9):
1497 - 1507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Alam, J. Weck, E. Maizels, Y. Park, E. J. Lee, M. Ashcroft, and M. Hunzicker-Dunn
Role of the Phosphatidylinositol-3-Kinase and Extracellular Regulated Kinase Pathways in the Induction of Hypoxia-Inducible Factor (HIF)-1 Activity and the HIF-1 Target Vascular Endothelial Growth Factor in Ovarian Granulosa Cells in Response to Follicle-Stimulating Hormone
Endocrinology,
February 1, 2009;
150(2):
915 - 928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Rosairo, I. Kuyznierewicz, J. Findlay, and A. Drummond
Transforming growth factor-{beta}: its role in ovarian follicle development
Reproduction,
December 1, 2008;
136(6):
799 - 809.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pelusi, Y. Ikeda, M. Zubair, and K. L. Parker
Impaired Follicle Development and Infertility in Female Mice Lacking Steroidogenic Factor 1 in Ovarian Granulosa Cells
Biol Reprod,
December 1, 2008;
79(6):
1074 - 1083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kyronlahti, M. Ramo, M. Tamminen, L. Unkila-Kallio, R. Butzow, A. Leminen, M. Nemer, N. Rahman, I. Huhtaniemi, M. Heikinheimo, et al.
GATA-4 Regulates Bcl-2 Expression in Ovarian Granulosa Cell Tumors
Endocrinology,
November 1, 2008;
149(11):
5635 - 5642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Fan, Z. Liu, N. Cahill, and J. S. Richards
Targeted Disruption of Pten in Ovarian Granulosa Cells Enhances Ovulation and Extends the Life Span of Luteal Cells
Mol. Endocrinol.,
September 1, 2008;
22(9):
2128 - 2140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Chen, M.-T. Lee, H.-C. Yao, P.-W. Hsiao, F.-C. Ke, and J.-J. Hwang
Crucial Role of Estrogen Receptor-{alpha} Interaction with Transcription Coregulators in Follicle-Stimulating Hormone and Transforming Growth Factor {beta}1 Up-Regulation of Steroidogenesis in Rat Ovarian Granulosa Cells
Endocrinology,
September 1, 2008;
149(9):
4658 - 4668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Fielenbach and A. Antebi
C. elegans dauer formation and the molecular basis of plasticity
Genes & Dev.,
August 15, 2008;
22(16):
2149 - 2165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Fan, M. Shimada, Z. Liu, N. Cahill, N. Noma, Y. Wu, J. Gossen, and J. S. Richards
Selective expression of KrasG12D in granulosa cells of the mouse ovary causes defects in follicle development and ovulation
Development,
June 15, 2008;
135(12):
2127 - 2137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Takano, Z. Lu, T. Goto, L. Fusi, J. Higham, J. Francis, A. Withey, J. Hardt, B. Cloke, A. V. Stavropoulou, et al.
Transcriptional Cross Talk between the Forkhead Transcription Factor Forkhead Box O1A and the Progesterone Receptor Coordinates Cell Cycle Regulation and Differentiation in Human Endometrial Stromal Cells
Mol. Endocrinol.,
October 1, 2007;
21(10):
2334 - 2349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Looyenga and G. D. Hammer
Genetic Removal of Smad3 from Inhibin-Null Mice Attenuates Tumor Progression by Uncoupling Extracellular Mitogenic Signals from the Cell Cycle Machinery
Mol. Endocrinol.,
October 1, 2007;
21(10):
2440 - 2457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D Rudd, I. Gonzalez-Robayna, I. Hernandez-Gonzalez, N. L Weigel, W. E Bingman III, and J. S Richards
Constitutively active FOXO1a and a DNA-binding domain mutant exhibit distinct co-regulatory functions to enhance progesterone receptor A activity
J. Mol. Endocrinol.,
June 1, 2007;
38(6):
673 - 690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Neganova, H. Al-Qassab, H. Heffron, C. Selman, A. I. Choudhury, S. J. Lingard, I. Diakonov, M. Patterson, M. Ghatei, S. R. Bloom, et al.
Role of Central Nervous System and Ovarian Insulin Receptor Substrate 2 Signaling in Female Reproductive Function in the Mouse
Biol Reprod,
June 1, 2007;
76(6):
1045 - 1053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A Glauser and W. Schlegel
The emerging role of FOXO transcription factors in pancreatic {beta} cells
J. Endocrinol.,
May 1, 2007;
193(2):
195 - 207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Chen, P.-W. Hsiao, M.-T. Lee, J I. Mason, F.-C. Ke, and J.-J. Hwang
Interplay of PI3K and cAMP/PKA signaling, and rapamycin-hypersensitivity in TGF{beta}1 enhancement of FSH-stimulated steroidogenesis in rat ovarian granulosa cells
J. Endocrinol.,
February 1, 2007;
192(2):
405 - 419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Onuma, B. T. Vander Kooi, J. N. Boustead, J. K. Oeser, and R. M. O'Brien
Correlation between FOXO1a (FKHR) and FOXO3a (FKHRL1) Binding and the Inhibition of Basal Glucose-6-Phosphatase Catalytic Subunit Gene Transcription by Insulin
Mol. Endocrinol.,
November 1, 2006;
20(11):
2831 - 2847.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. N. Parakh, J. A. Hernandez, J. C. Grammer, J. Weck, M. Hunzicker-Dunn, A. J. Zeleznik, and J. H. Nilson
Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin
PNAS,
August 15, 2006;
103(33):
12435 - 12440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Muniz, G. Yehia, E. Memin, P. V.A.L. Ratnakar, and C. A. Molina
Transcriptional Regulation of Cyclin D2 by the PKA Pathway and Inducible cAMP Early Repressor in Granulosa Cells
Biol Reprod,
August 1, 2006;
75(2):
279 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Pangas, X. Li, E. J. Robertson, and M. M. Matzuk
Premature Luteinization and Cumulus Cell Defects in Ovarian-Specific Smad4 Knockout Mice
Mol. Endocrinol.,
June 1, 2006;
20(6):
1406 - 1422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Kayampilly and K. M. J. Menon
Dihydrotestosterone Inhibits Insulin-Stimulated Cyclin D2 Messenger Ribonucleic Acid Expression in Rat Ovarian Granulosa Cells by Reducing the Phosphorylation of Insulin Receptor Substrate-1
Endocrinology,
January 1, 2006;
147(1):
464 - 471.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|
