This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carvalho, C. R. O. Articles by Saad, M. J. A. Search for Related Content PubMed PubMed Citation Articles by Carvalho, C. R. O. Articles by Saad, M. J. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Dietary Proteins Hazardous Substances DB L-TYROSINE

Novel Signal Transduction Pathway for Luteinizing Hormone and Its Interaction with Insulin: Activation of Janus Kinase/Signal Transducer and Activator of Transcription and Phosphoinositol 3-Kinase/Akt Pathways

Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (J.B.C.C., M.H.M.L., S.F.Z., A.L.G., V.M., L.F.Z., L.A.V., M.J.A.S.), 13081-970 Campinas, Brazil; and Departamento de Fisiologia e Biofisica, Instituto de Ciências Biomédicas, Universidade de São Paulo (C.R.O.C., L.C.C., A.A.), 13081-970 São Paulo, Brazil

Address all correspondence and requests for reprints to: Mario J. A. Saad, M.D., Departamento de Clínica Médica, Faculdade de Ciências Médicas-Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, 13081-970 Campinas, Brazil. E-mail: msaad{at}fcm.unicamp.br.

The actions of LH are mediated through a single class of cell surface LH/human chorionic gonadotropin receptor, which is a member of the G protein-coupled receptor family. In the present study we showed that LH induced rapid tyrosine phosphorylation and activation of the Janus kinase 2 (JAK2) in rat ovary. Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc /growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. The simultaneous infusion of insulin and LH induced higher phosphorylation levels of JAK2, STAT5b, IRS-1, and AKT compared with each hormone alone in the whole ovary of normal rats. By immunohistochemistry we demonstrated that these late events take place in follicular cells and both external and internal theca. These results indicate a new signal transduction pathway for LH and show that there is positive cross-talk between the insulin and LH signaling pathways at the level of phosphoinositol 3-kinase/AKT pathway in this tissue.

This article has been cited by other articles:

				K. Shkolnik, S. Ben-Dor, D. Galiani, A. Hourvitz, and N. Dekel Molecular characterization and bioinformatics analysis of Ncoa7B, a novel ovulation-associated and reproduction system-specific Ncoa7 isoform Reproduction, March 1, 2008; 135(3): 321 - 333. [Abstract] [Full Text] [PDF]

				G.-S. Hwang, S.-W. Wang, W.-M. Tseng, C.-H. Yu, and P. S. Wang Effect of hypoxia on the release of vascular endothelial growth factor and testosterone in mouse TM3 Leydig cells Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1763 - E1769. [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]

				H. G. Zecchin, F. B.M. Priviero, C. T. Souza, K. G. Zecchin, P. O. Prada, J. B.C. Carvalheira, L. A. Velloso, E. Antunes, and M. J.A. Saad Defective Insulin and Acetylcholine Induction of Endothelial Cell-Nitric Oxide Synthase Through Insulin Receptor Substrate/Akt Signaling Pathway in Aorta of Obese Rats Diabetes, April 1, 2007; 56(4): 1014 - 1024. [Abstract] [Full Text] [PDF]

				L. S. Sleer and C. C. Taylor Platelet-Derived Growth Factors and Receptors in the Rat Corpus Luteum: Localization and Identification of an Effect on Luteogenesis Biol Reprod, March 1, 2007; 76(3): 391 - 400. [Abstract] [Full Text] [PDF]

				M. Jo and T. E. Curry Jr. Luteinizing Hormone-Induced RUNX1 Regulates the Expression of Genes in Granulosa Cells of Rat Periovulatory Follicles Mol. Endocrinol., September 1, 2006; 20(9): 2156 - 2172. [Abstract] [Full Text] [PDF]

				M. I. Hernandez, A. Martinez, T. Capurro, V. Pena, L. Trejo, A. Avila, T. Salazar, S. Asenjo, G. Iniguez, and V. Mericq Comparison of Clinical, Ultrasonographic, and Biochemical Differences at the Beginning of Puberty in Healthy Girls Born Either Small for Gestational Age or Appropriate for Gestational Age: Preliminary Results J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3377 - 3381. [Abstract] [Full Text] [PDF]

				M. H M Lima, L. C Souza, L. C Caperuto, E. Bevilacqua, A. L Gasparetti, R. Zanuto, M. J A Saad, and C. R O Carvalho Up-regulation of the phosphatidylinositol 3-kinase/protein kinase B pathway in the ovary of rats by chronic treatment with hCG and insulin. J. Endocrinol., August 1, 2006; 190(2): 451 - 459. [Abstract] [Full Text] [PDF]

				E. R. Gross, A. K. Hsu, and G. J. Gross The JAK/STAT pathway is essential for opioid-induced cardioprotection: JAK2 as a mediator of STAT3, Akt, and GSK-3beta Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H827 - H834. [Abstract] [Full Text] [PDF]

				K. Shiraishi and M. Ascoli Activation of the Lutropin/Choriogonadotropin Receptor in MA-10 Cells Stimulates Tyrosine Kinase Cascades that Activate Ras and the Extracellular Signal Regulated Kinases (ERK1/2) Endocrinology, July 1, 2006; 147(7): 3419 - 3427. [Abstract] [Full Text] [PDF]

				J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C.K. Leung Gonadotropins Activate Proteolysis and Increase Invasion through Protein Kinase A and Phosphatidylinositol 3-Kinase Pathways in Human Epithelial Ovarian Cancer Cells. Cancer Res., April 1, 2006; 66(7): 3912 - 3920. [Abstract] [Full Text] [PDF]

				F. X. Donadeu and M. Ascoli The Differential Effects of the Gonadotropin Receptors on Aromatase Expression in Primary Cultures of Immature Rat Granulosa Cells Are Highly Dependent on the Density of Receptors Expressed and the Activation of the Inositol Phosphate Cascade Endocrinology, September 1, 2005; 146(9): 3907 - 3916. [Abstract] [Full Text] [PDF]

				K. Tajima, K. Yoshii, S. Fukuda, M. Orisaka, K. Miyamoto, A. Amsterdam, and F. Kotsuji Luteinizing Hormone-Induced Extracellular-Signal Regulated Kinase Activation Differently Modulates Progesterone and Androstenedione Production in Bovine Theca Cells Endocrinology, July 1, 2005; 146(7): 2903 - 2910. [Abstract] [Full Text] [PDF]

				J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C K Leung Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human ovarian surface epithelial cells Endocr. Relat. Cancer, June 1, 2005; 12(2): 407 - 421. [Abstract] [Full Text] [PDF]

				H. Zhou, Y. Jiang, W. K W Ko, W. Li, and A. O L Wong Paracrine regulation of growth hormone gene expression by gonadotrophin release in grass carp pituitary cells: functional implications, molecular mechanisms and signal transduction J. Mol. Endocrinol., April 1, 2005; 34(2): 415 - 432. [Abstract] [Full Text] [PDF]

				M. I. C. Alonso-Vale, S. Andreotti, S. B. Peres, G. F. Anhe, C. das Neves Borges-Silva, J. C. Neto, and F. B. Lima Melatonin enhances leptin expression by rat adipocytes in the presence of insulin Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E805 - E812. [Abstract] [Full Text] [PDF]

				B. Ahr, M. Denizot, V. Robert-Hebmann, A. Brelot, and M. Biard-Piechaczyk Identification of the Cytoplasmic Domains of CXCR4 Involved in Jak2 and STAT3 Phosphorylation J. Biol. Chem., February 25, 2005; 280(8): 6692 - 6700. [Abstract] [Full Text] [PDF]

				V. L. Nelson-Degrave, J. K. Wickenheisser, K. L. Hendricks, T. Asano, M. Fujishiro, R. S. Legro, S. R. Kimball, J. F. Strauss III, and J. M. McAllister Alterations in Mitogen-Activated Protein Kinase Kinase and Extracellular Regulated Kinase Signaling in Theca Cells Contribute to Excessive Androgen Production in Polycystic Ovary Syndrome Mol. Endocrinol., February 1, 2005; 19(2): 379 - 390. [Abstract] [Full Text] [PDF]

				S. Rice, N. Christoforidis, C. Gadd, D. Nikolaou, L. Seyani, A. Donaldson, R. Margara, K. Hardy, and S. Franks Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries Hum. Reprod., February 1, 2005; 20(2): 373 - 381. [Abstract] [Full Text] [PDF]

				K.M.J. Menon, U. M. Munshi, C. L. Clouser, and A. K. Nair Regulation of Luteinizing Hormone/Human Chorionic Gonadotropin Receptor Expression: A Perspective Biol Reprod, April 1, 2004; 70(4): 861 - 866. [Abstract] [Full Text] [PDF]