| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Molecular and Cellular Biology (M.S., I.H.-G., I.G.-R., J.S.R.), Baylor College of Medicine, Houston, Texas 77030; Department of Applied Animal Science (M.S.), Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 724-8528, Japan; and Departments of Biochemistry and Molecular Biology and Physiology (I.H.-G., I.G.-R.), Faculty of Sciences, University of Las Palmas, 35016 Las Palmas Grand Canaria, Spain
Address all correspondence and requests for reprints to: JoAnne S. Richards, Ph.D., Professor, Department of Molecular Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: joanner{at}bcm.tmc.edu.
The molecular bridges that link the LH surge with functional changes in cumulus cells that possess few LH receptors are being unraveled. Herein we document that epidermal growth factor (EGF)-like factors amphiregulin (Areg), epiregulin (Ereg), and betacellulin (Btc) are induced in cumulus oocyte complexes (COCs) by autocrine and paracrine mechanisms that involve the actions of prostaglandins (PGs) and progesterone receptor (PGR). Areg and Ereg mRNA and protein levels were reduced significantly in COCs and ovaries collected from prostaglandin synthase 2 (Ptgs2) null mice and Pgr null (PRKO) mice at 4 h and 8 h after human chorionic gonadotropin, respectively. In cultured COCs, FSH/forskolin induced Areg mRNA within 0.5 h that peaked at 4 h, a process blocked by inhibitors of p38MAPK (SB203580), MAPK kinase (MEK) 1 (PD98059), and PTGS2 (NS398) but not protein kinase A (PKA) (KT5720). Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF receptor tyrosine kinase inhibitor AG1478 (AG), PD98059, and NS398. PGE2 reversed the inhibitory effects of AG on AREG-induced expression of Areg but not Ptgs2, placing Ptgs2 downstream of EGF-R signaling. Phorbol 12-myristate 13-acetate (PMA) and adenovirally expressed PGRA synergistically induced Areg mRNA in granulosa cells. In COCs, AREG not only induced genes that impact matrix formation but also genes involved in steroidogenesis (StAR, Cyp11a1) and immune cell-like functions (Pdcd1, Runx1, Cd52). Collectively, FSH-mediated induction of Areg mRNA via p38MAPK precedes AREG induction of Ptgs2 mRNA via ERK1/2. PGs acting via PTGER2 in cumulus cells provide a secondary, autocrine pathway to regulate expression of Areg in COCs showing critical functional links between G protein-coupled receptor and growth factor receptor pathways in ovulating follicles.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  T. da Silva Faria, F. de Bittencourt Brasil, F. J B Sampaio, and C. da Fonte Ramos Maternal malnutrition during lactation alters the folliculogenesis and gonadotropins and estrogen isoforms ovarian receptors in the offspring at puberty J. Endocrinol., September 1, 2008; 198(3): 625 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kawashima, T. Okazaki, N. Noma, M. Nishibori, Y. Yamashita, and M. Shimada Sequential exposure of porcine cumulus cells to FSH and/or LH is critical for appropriate expression of steroidogenic and ovulation-related genes that impact oocyte maturation in vivo and in vitro Reproduction, July 1, 2008; 136(1): 9 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ning, H. Ouyang, S. Wang, X. Chen, B. Xu, J. Yang, H. Zhang, M. Zhang, and G. Xia 3',5'-Cyclic Adenosine Monophosphate Response Element Binding Protein Up-Regulated Cytochrome P450 Lanosterol 14{alpha}-Demethylase Expression Involved in Follicle-Stimulating Hormone-Induced Mouse Oocyte Maturation Mol. Endocrinol., July 1, 2008; 22(7): 1682 - 1694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wakamatsu, J. B. Collins, J. S. Parker, M. Tessema, N. P. Clayton, T.-V. T. Ton, H.-H. L. Hong, S. Belinsky, T. R. Devereux, R. C. Sills, et al. Gene Expression Studies Demonstrate that the K-ras/Erk MAP Kinase Signal Transduction Pathway and Other Novel Pathways Contribute to the Pathogenesis of Cumene-induced Lung Tumors Toxicol Pathol, July 1, 2008; 36(5): 743 - 752. [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]
|
|
|
|
 |
|
 E.-S. Park, S. Choi, K. N. Muse, T. E. Curry Jr., and M. Jo Response Gene to Complement 32 Expression Is Induced by the Luteinizing Hormone (LH) Surge and Regulated by LH-Induced Mediators in the Rodent Ovary Endocrinology, June 1, 2008; 149(6): 3025 - 3036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, B. Zhou, J. Yan, B. Xu, P. Tai, J. Li, S. Peng, M. Zhang, and G. Xia Epidermal growth factor receptor activation by protein kinase C is necessary for FSH-induced meiotic resumption in porcine cumulus-oocyte complexes J. Endocrinol., May 1, 2008; 197(2): 409 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Nuttinck, B. M.-L. Guienne, L. Clement, P. Reinaud, G. Charpigny, and B. Grimard Expression of genes involved in prostaglandin E2 and progesterone production in bovine cumulus-oocyte complexes during in vitro maturation and fertilization Reproduction, May 1, 2008; 135(5): 593 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Nagyova, A. Camaioni, R. Prochazka, A. J. Day, and A. Salustri Synthesis of Tumor Necrosis Factor Alpha-Induced Protein 6 in Porcine Preovulatory Follicles: A Study with A38 Antibody Biol Reprod, May 1, 2008; 78(5): 903 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Panigone, M. Hsieh, M. Fu, L. Persani, and M. Conti Luteinizing Hormone Signaling in Preovulatory Follicles Involves Early Activation of the Epidermal Growth Factor Receptor Pathway Mol. Endocrinol., April 1, 2008; 22(4): 924 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A Gratao, M. Dahlhoff, F. Sinowatz, E. Wolf, and M. R Schneider Betacellulin Overexpression in the Mouse Ovary Leads to MAPK3/MAPK1 Hyperactivation and Reduces Litter Size by Impairing Fertilization Biol Reprod, January 1, 2008; 78(1): 43 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamashita, I. Kawashima, Y. Yanai, M. Nishibori, J. S. Richards, and M. Shimada Hormone-Induced Expression of Tumor Necrosis Factor {alpha}-Converting Enzyme/A Disintegrin and Metalloprotease-17 Impacts Porcine Cumulus Cell Oocyte Complex Expansion and Meiotic Maturation via Ligand Activation of the Epidermal Growth Factor Receptor Endocrinology, December 1, 2007; 148(12): 6164 - 6175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Feuerstein, V. Cadoret, R. Dalbies-Tran, F. Guerif, R. Bidault, and D. Royere Gene expression in human cumulus cells: one approach to oocyte competence Hum. Reprod., December 1, 2007; 22(12): 3069 - 3077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xie, H. Wang, S. Tranguch, R. Iwamoto, E. Mekada, F. J. DeMayo, J. P. Lydon, S. K. Das, and S. K. Dey Maternal heparin-binding-EGF deficiency limits pregnancy success in mice PNAS, November 13, 2007; 104(46): 18315 - 18320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimada, Y. Yanai, T. Okazaki, Y. Yamashita, V. Sriraman, M. C. Wilson, and J. S. Richards Synaptosomal-Associated Protein 25 Gene Expression Is Hormonally Regulated during Ovulation and Is Involved in Cytokine/Chemokine Exocytosis from Granulosa Cells Mol. Endocrinol., October 1, 2007; 21(10): 2487 - 2502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-G. Liang, Y.-Q. Su, H.-Y. Fan, H. Schatten, and Q.-Y. Sun Mechanisms Regulating Oocyte Meiotic Resumption: Roles of Mitogen-Activated Protein Kinase Mol. Endocrinol., September 1, 2007; 21(9): 2037 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, J. Li, C. Ying Wang, A. H. Yan Kwok, and F. C. Leung Epidermal Growth Factor (EGF) Receptor Ligands in the Chicken Ovary: I. Evidence for Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Potential Oocyte-Derived Signal to Control Granulosa Cell Proliferation and HB-EGF and Kit Ligand Expression Endocrinology, July 1, 2007; 148(7): 3426 - 3440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.N. Fru, M. Cherian-Shaw, M. Puttabyatappa, C.A. VandeVoort, and C.L. Chaffin Regulation of granulosa cell proliferation and EGF-like ligands during the periovulatory interval in monkeys Hum. Reprod., May 1, 2007; 22(5): 1247 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C Woods and A L Johnson Protein kinase C activity mediates LH-induced ErbB/Erk signaling in differentiated hen granulosa cells Reproduction, April 1, 2007; 133(4): 733 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sasseville, N. Cote, C. Vigneault, C. Guillemette, and F. J. Richard 3'5'-Cyclic Adenosine Monophosphate-Dependent Up-Regulation of Phosphodiesterase Type 3A in Porcine Cumulus Cells Endocrinology, April 1, 2007; 148(4): 1858 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hsieh, D. Lee, S. Panigone, K. Horner, R. Chen, A. Theologis, D. C. Lee, D. W. Threadgill, and M. Conti Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation Mol. Cell. Biol., March 1, 2007; 27(5): 1914 - 1924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Takahashi, J. D. Morrow, H. Wang, and S. K. Dey Cyclooxygenase-2-derived Prostaglandin E2 Directs Oocyte Maturation by Differentially Influencing Multiple Signaling Pathways J. Biol. Chem., December 1, 2006; 281(48): 37117 - 37129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Q. Su, M. Nyegaard, M. T. Overgaard, J. Qiao, and L. C. Giudice Participation of Mitogen-Activated Protein Kinase in Luteinizing Hormone-Induced Differential Regulation of Steroidogenesis and Steroidogenic Gene Expression in Mural and Cumulus Granulosa Cells of Mouse Preovulatory Follicles Biol Reprod, December 1, 2006; 75(6): 859 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Yoshino, H. E. McMahon, S. Sharma, and S. Shimasaki A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse PNAS, July 11, 2006; 103(28): 10678 - 10683. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
