| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mechanisms of Hormone Action |
Unité de Physiologie de la Reproduction et des Comportements,2 UMR INRA-CNRS, 37380 Nouzilly, France
Medical Research Council Human Reproductive Sciences Unit,3 Center for Reproductive Biology, Edinburgh EH16 4SB, United Kingdom
Centre de Recherches de Jouy,4 Département de Génétique Animale, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France
In the pituitary, activin stimulates the synthesis and release of FSH. However, the activin receptor signaling pathways that mediate these effects are poorly known. We investigated these mechanisms in primary ovine pituitary cells (POP) and in the murine LßT2 gonadotrope cell line. POP cells and LßT2 cells express the different activin receptors (types IA, IB, IIA, and IIB) and the Smad proteins (Smad-2, -3, -4, and -7). In both POP and LßT2 cells, activin activated several signaling pathways: Smad-2, extracellular regulated kinase-1/2 (ERK1/2), p38, and phosphatidylinositol 3'-kinase (PI3K)/Akt. Phosphorylation of ERK1/2 and p38 were stimulated (3- to 6-fold) rapidly in 5 min, whereas activation of both Smad-2 and Akt (3- to 5-fold) occurred later, in 60 min. Activin also increased the association of activin receptor IIB with PI3K. Using specific inhibitors, we demonstrated that the activation of Smad-2 was partially blocked by the inhibition of PI3K but not by the inhibition of ERK1/2 or p38, suggesting a cross-talk between the Smad and PI3K/Akt pathways. In both POP and LßT2 cells, FSH expression and secretion in response to activin were not altered by the inhibition of PI3K/Akt, ERK1/2, or p38 pathways, whereas they were reduced by about 2-fold by expression of a dominant negative of Smad-2 or the natural inhibitory Smad-7 in LßT2 cells. These results indicate that activin activates several signaling pathways with different time courses in both POP and LßT2 cells, but only the Smad-2 pathway appears to be directly implicated in FSH expression and release in LßT2 cells.
This article has been cited by other articles:
|
|
 |
|
  P. Lamba, J. Fortin, S. Tran, Y. Wang, and D. J. Bernard A Novel Role for the Forkhead Transcription Factor FOXL2 in Activin A-Regulated Follicle-Stimulating Hormone {beta} Subunit Transcription Mol. Endocrinol., July 1, 2009; 23(7): 1001 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Ho and D. J. Bernard Bone Morphogenetic Protein 2 Signals via BMPR1A to Regulate Murine Follicle-Stimulating Hormone Beta Subunit Transcription Biol Reprod, July 1, 2009; 81(1): 133 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-V. Do, L. A. Kubba, M. Antenos, A. W. Rademaker, C. D. Sturgis, and T. K. Woodruff The Role of Activin A and Akt/GSK Signaling in Ovarian Tumor Biology Endocrinology, August 1, 2008; 149(8): 3809 - 3816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Robin, J Cognie, F Foulon-Gauze, J Fontaine, and X Cayla Disruption of Lipid Rafts Induces Gonadotropin Release in Ovine Pituitary and LbetaT2 Gonadotroph Cells Biol Reprod, July 1, 2008; 79(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Manikkam, R. C. Thompson, C. Herkimer, K. B. Welch, J. Flak, F. J. Karsch, and V. Padmanabhan Developmental Programming: Impact of Prenatal Testosterone Excess on Pre- and Postnatal Gonadotropin Regulation in Sheep Biol Reprod, April 1, 2008; 78(4): 648 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Nicol, M-O Faure, J R McNeilly, J Fontaine, C Taragnat, and A S McNeilly Bone morphogenetic protein-4 interacts with activin and GnRH to modulate gonadotrophin secretion in L{beta}T2 gonadotrophs J. Endocrinol., March 1, 2008; 196(3): 497 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Thackray and P. L. Mellon Synergistic Induction of Follicle-Stimulating Hormone {beta}-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smad Proteins Endocrinology, March 1, 2008; 149(3): 1091 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Kipp, S. M. Kilen, T. K. Woodruff, and K. E. Mayo Activin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary J. Biol. Chem., December 14, 2007; 282(50): 36755 - 36765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Chand, G. T. Ooi, C. A. Harrison, A. N. Shelling, and D. M. Robertson Functional analysis of the human inhibin {alpha} subunit variant A257T and its potential role in premature ovarian failure Hum. Reprod., December 1, 2007; 22(12): 3241 - 3248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Burger, D. J. Haisenleder, G. M. Wotton, K. W. Aylor, A. C. Dalkin, and J. C. Marshall The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E277 - E285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Lawson, R. Tsutsumi, H. Zhang, I. Talukdar, B. K. Butler, S. J. Santos, P. L. Mellon, and N. J. G. Webster Pulse Sensitivity of the Luteinizing Hormone {beta} Promoter Is Determined by a Negative Feedback Loop Involving Early Growth Response-1 and Ngfi-A Binding Protein 1 and 2 Mol. Endocrinol., May 1, 2007; 21(5): 1175 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B Lee, V. Khivansara, M. M Santos, P. Lamba, T. Yuen, S. C Sealfon, and D. J Bernard Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone {beta} subunit transcription J. Mol. Endocrinol., February 1, 2007; 38(2): 315 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, J. S. Bailey, D. Coss, B. Lin, R. Tsutsumi, M. A. Lawson, P. L. Mellon, and N. J. G. Webster Activin Modulates the Transcriptional Response of LssT2 Cells to Gonadotropin-Releasing Hormone and Alters Cellular Proliferation Mol. Endocrinol., November 1, 2006; 20(11): 2909 - 2930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G Farnworth, Y. Wang, P. Leembruggen, G. T Ooi, C. Harrison, D. M Robertson, and J. K Findlay Rodent adrenocortical cells display high affinity binding sites and proteins for inhibin A, and express components required for autocrine signalling by activins and bone morphogenetic proteins. J. Endocrinol., March 1, 2006; 188(3): 451 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lamba, M. M Santos, D. P Philips, and D. J Bernard Acute regulation of murine follicle-stimulating hormone {beta} subunit transcription by activin A J. Mol. Endocrinol., February 1, 2006; 36(1): 201 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M-O Faure, L Nicol, S Fabre, J Fontaine, N Mohoric, A McNeilly, and C Taragnat BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary J. Endocrinol., July 1, 2005; 186(1): 109 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Suszko, D. M. Balkin, Y. Chen, and T. K. Woodruff Smad3 Mediates Activin-Induced Transcription of Follicle-Stimulating Hormone {beta}-Subunit Gene Mol. Endocrinol., July 1, 2005; 19(7): 1849 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Gregory, C. T. Lacza, A. A. Detz, S. Xu, L. A. Petrillo, and U. B. Kaiser Synergy between Activin A and Gonadotropin-Releasing Hormone in Transcriptional Activation of the Rat Follicle-Stimulating Hormone-{beta} Gene Mol. Endocrinol., January 1, 2005; 19(1): 237 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall Regulation of gonadotropin subunit gene transcription J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Bailey, N. Rave-Harel, S. M. McGillivray, D. Coss, and P. L. Mellon Activin Regulation of the Follicle-Stimulating Hormone {beta}-Subunit Gene Involves Smads and the TALE Homeodomain Proteins Pbx1 and Prep1 Mol. Endocrinol., May 1, 2004; 18(5): 1158 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Bernard Both SMAD2 and SMAD3 Mediate Activin-Stimulated Expression of the Follicle-Stimulating Hormone {beta} Subunit in Mouse Gonadotrope Cells Mol. Endocrinol., March 1, 2004; 18(3): 606 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Runyan, H. W. Schnaper, and A.-C. Poncelet The Phosphatidylinositol 3-Kinase/Akt Pathway Enhances Smad3-stimulated Mesangial Cell Collagen I Expression in Response to Transforming Growth Factor-{beta}1 J. Biol. Chem., January 23, 2004; 279(4): 2632 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamada, H. Yamamoto, T. Yonehara, H. Kanasaki, H. Nakanishi, E. Miyamoto, and K. Miyazaki Differential Activation of the Luteinizing Hormone {beta}-Subunit Promoter by Activin and Gonadotropin-Releasing Hormone: A Role for the Mitogen-Activated Protein Kinase Signaling Pathway in L{beta}T2 Gonadotrophs Biol Reprod, January 1, 2004; 70(1): 236 - 243. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
