| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 12, 2004
Accepted on October 7, 2004
Department of Biochemistry and Molecular Genetics, School of Medicine, P.O. Box 800733, University of Virginia, Charlottesville, VA 22908-0733; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
* To whom correspondence should be addressed. E-mail: yh4b{at}virginia.edu.
Ovarian granulosa cells play pivotal roles in many aspects of ovary functions including folliculogenesis and steroidogenesis. In response to follicle stimulating hormone (FSH) and LH (LH), the elevation of intracellular cyclic AMP (cAMP) level in granulosa cells leads to activation of multiple ovarian genes. Here we report findings from a genome-wide study of the cAMP-responsive gene expression profiles in a human granulosa-like tumor cell line, KGN. The study identified 140 genes that are either activated or repressed by 2-fold or greater following stimulation by the adenylyl cyclase activator forskolin. The induction patterns of some cAMP-responsive genes were further analyzed by quantitative real time PCR. Consistent with previous observations, the LH-responsive genes such as the nuclear receptor 4A subfamily (NURR1, NGFI-B, and NOR-1) were rapidly but transiently induced, whereas the FSH-responsive gene CYP19 encoding aromatase was induced in a delayed fashion. Interestingly, ectopic expression of NURR1 or NGFI-B severely attenuated the cAMP-responsive activation of the ovary-specific aromatase promoter. Reduction of the endogenous NURR1 or NGFI-B by small interfering RNA (siRNA) significantly elevated aromatase gene expression. The cis-elements responsible for NURR1/NGFI-B-mediated repression were mapped to the minimal aromatase promoter sequence that confers cAMP-responsiveness. Furthermore, the DNA-binding domain of NURR1 was required for the repression. Taken together, these results strongly suggest a causal relationship between the rapid decline of aromatase mRNA and induction of NR4A expression that concomitantly occur upon LH surge at the later stages of ovarian follicular development.
This article has been cited by other articles:
 |
|
 |
|
  K. S. Mix, M. G. Attur, H. Al-Mussawir, S. B. Abramson, C. E. Brinckerhoff, and E. P. Murphy Transcriptional Repression of Matrix Metalloproteinase Gene Expression by the Orphan Nuclear Receptor NURR1 in Cartilage J. Biol. Chem., March 30, 2007; 282(13): 9492 - 9504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lu, A. Amleh, J. Sun, X. Jin, S. D. McCullough, R. Baer, D. Ren, R. Li, and Y. Hu Ubiquitination and Proteasome-Mediated Degradation of BRCA1 and BARD1 during Steroidogenesis in Human Ovarian Granulosa Cells Mol. Endocrinol., March 1, 2007; 21(3): 651 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Miyoshi, F. Otsuka, J. Suzuki, M. Takeda, K. Inagaki, Y. Kano, H. Otani, Y. Mimura, T. Ogura, and H. Makino Mutual Regulation of Follicle-Stimulating Hormone Signaling and Bone Morphogenetic Protein System in Human Granulosa Cells Biol Reprod, June 1, 2006; 74(6): 1073 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. R. Holla, J. R. Mann, Q. Shi, and R. N. DuBois Prostaglandin E2 Regulates the Nuclear Receptor NR4A2 in Colorectal Cancer J. Biol. Chem., February 3, 2006; 281(5): 2676 - 2682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Couse, M. M. Yates, B. J. Deroo, and K. S. Korach Estrogen Receptor-{beta} Is Critical to Granulosa Cell Differentiation and the Ovulatory Response to Gonadotropins Endocrinology, August 1, 2005; 146(8): 3247 - 3262. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
