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 Salvador, L. M. Articles by Hunzicker-Dunn, M. Search for Related Content PubMed PubMed Citation Articles by Salvador, L. M. Articles by Hunzicker-Dunn, M.

Acute Signaling by the LH Receptor Is Independent of Protein Kinase C Activation

Departments of Cell and Molecular Biology, Northwestern University Medical School (L.M.S., E.M., M.H.-D.), Chicago, Illinois 60611; Department of Physiology and Biophysics, University of Illinois School of Medicine (D.B.H.), Chicago, Illinois 60611; and Department of Pharmacology, Kumamoto University School of Medicine (E.M., H.Y.), 2-2-1 Honjo, Kumamoto 860-0811, Japan

Address all correspondence and requests for reprints to: Dr. Mary Hunzicker-Dunn, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611. E-mail: . mhd{at}northwestern.edu

LH receptor activation leads to the phosphorylation/activation of p42/44 MAPK in preovulatory granulosa cells. As the LH receptor can activate both adenylyl cyclase and phospholipase C, we hypothesized that the LH receptor could elicit phosphorylation of p42/44 MAPK through activation of protein kinase A (PKA) and/or protein kinase C (PKC). Preovulatory granulosa cells in serum-free primary cultures were treated with ovulatory concentrations of human chorionic gonadotropin (hCG), an LH receptor agonist, with or without various inhibitors. The PKA inhibitor H89 as well as the myristoylated PKA inhibitor peptide PKI strongly inhibited hCG-stimulated p42/44 MAPK phosphorylation, whereas the PKC inhibitor GF109203X had no effect on p42/44 MAPK phosphorylation. LH receptor-stimulated phosphorylation of cAMP response element-binding protein (CREB), histone H3, and MAPK kinase (MEK) was also strongly inhibited by H89 and not by GF109203X. The extent of PKC activation was assessed in preovulatory granulosa cells using three criteria: translocation of PKC isoforms to the membrane fraction, phosphorylation of a known PKC substrate, and autophosphorylation of PKC on an activation-related site. By all three criteria PKCs were partially activated before hCG stimulation, and hCG treatment failed to elicit further PKC activation, in vitro or in vivo. Taken together, these results indicate that, under primary culture conditions where physiological levels of signaling proteins are present, hCG signals to activate MEK, p42/44 MAPK, CREB, and histone H3 in a predominately PKA-dependent and PKC-independent manner. Unexpectedly, PKCs were partially activated in the absence of LH receptor activation, and LH receptor activation did not elicit further detectable PKC activation.

This article has been cited by other articles:

				N. Andric and M. Ascoli The Luteinizing Hormone Receptor-Activated Extracellularly Regulated Kinase-1/2 Cascade Stimulates Epiregulin Release from Granulosa Cells Endocrinology, November 1, 2008; 149(11): 5549 - 5556. [Abstract] [Full Text] [PDF]

				M. P. Flynn, E. T. Maizels, A. B. Karlsson, T. McAvoy, J.-H. Ahn, A. C. Nairn, and M. Hunzicker-Dunn Luteinizing Hormone Receptor Activation in Ovarian Granulosa Cells Promotes Protein Kinase A-Dependent Dephosphorylation of Microtubule-Associated Protein 2D Mol. Endocrinol., July 1, 2008; 22(7): 1695 - 1710. [Abstract] [Full Text] [PDF]

				P. Zhao, A. De, Z. Hu, J. Li, S. M. Mulders, M. D. Sollewijn Gelpke, E.-K. Duan, and A. J. W. Hsueh Gonadotropin Stimulation of Ovarian Fractalkine Expression and Fractalkine Augmentation of Progesterone Biosynthesis by Luteinizing Granulosa Cells Endocrinology, June 1, 2008; 149(6): 2782 - 2789. [Abstract] [Full Text] [PDF]

				S. Sela-Abramovich, D. Galiani, N. Nevo, and N. Dekel Inhibition of Rat Oocyte Maturation and Ovulation by Nitric Oxide: Mechanism of Action Biol Reprod, June 1, 2008; 78(6): 1111 - 1118. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				K. Shiraishi and M. Ascoli Lutropin/Choriogonadotropin Stimulate the Proliferation of Primary Cultures of Rat Leydig Cells through a Pathway that Involves Activation of the Extracellularly Regulated Kinase 1/2 Cascade Endocrinology, July 1, 2007; 148(7): 3214 - 3225. [Abstract] [Full Text] [PDF]

				D. L. Russell and R. L. Robker Molecular mechanisms of ovulation: co-ordination through the cumulus complex Hum. Reprod. Update, May 1, 2007; 13(3): 289 - 312. [Abstract] [Full Text] [PDF]

				J. Kwintkiewicz, Z. Cai, and C. Stocco Follicle-Stimulating Hormone-Induced Activation of Gata4 Contributes in the Up-Regulation of Cyp19 Expression in Rat Granulosa Cells Mol. Endocrinol., April 1, 2007; 21(4): 933 - 947. [Abstract] [Full Text] [PDF]

				C. Stocco, C. Telleria, and G. Gibori The Molecular Control of Corpus Luteum Formation, Function, and Regression Endocr. Rev., February 1, 2007; 28(1): 117 - 149. [Abstract] [Full Text] [PDF]

				N. Andric and M. Ascoli A Delayed Gonadotropin-Dependent and Growth Factor-Mediated Activation of the Extracellular Signal-Regulated Kinase 1/2 Cascade Negatively Regulates Aromatase Expression in Granulosa Cells Mol. Endocrinol., December 1, 2006; 20(12): 3308 - 3320. [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]

				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]

				I. Ben-Ami, S. Freimann, L. Armon, A. Dantes, R. Ron-El, and A. Amsterdam Novel function of ovarian growth factors: combined studies by DNA microarray, biochemical and physiological approaches Mol. Hum. Reprod., July 1, 2006; 12(7): 413 - 419. [Abstract] [Full Text] [PDF]

				V. K. Yadav and R. Medhamurthy Dynamic Changes in Mitogen-Activated Protein Kinase (MAPK) Activities in the Corpus Luteum of the Bonnet Monkey (Macaca radiata) during Development, Induced Luteolysis, and Simulated Early Pregnancy: A Role for p38 MAPK in the Regulation of Luteal Function Endocrinology, April 1, 2006; 147(4): 2018 - 2027. [Abstract] [Full Text] [PDF]

				V. Sriraman, M. D. Rudd, S. M. Lohmann, S. M. Mulders, and J. S. Richards Cyclic Guanosine 5'-Monophosphate-Dependent Protein Kinase II Is Induced by Luteinizing Hormone and Progesterone Receptor-Dependent Mechanisms in Granulosa Cells and Cumulus Oocyte Complexes of Ovulating Follicles Mol. Endocrinol., February 1, 2006; 20(2): 348 - 361. [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]

				F.-Q. Yu, C.-S. Han, W. Yang, X. Jin, Z.-Y. Hu, and Y.-X. Liu Activation of the p38 MAPK pathway by follicle-stimulating hormone regulates steroidogenesis in granulosa cells differentially J. Endocrinol., July 1, 2005; 186(1): 85 - 96. [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. Jo, M. C. Gieske, C. E. Payne, S. E. Wheeler-Price, J. B. Gieske, I. V. Ignatius, T. E. Curry Jr., and C. Ko Development and Application of a Rat Ovarian Gene Expression Database Endocrinology, November 1, 2004; 145(11): 5384 - 5396. [Abstract] [Full Text] [PDF]

				L. M. Salvador, M. P. Flynn, J. Avila, S. Reierstad, E. T. Maizels, H. Alam, Y. Park, J. D. Scott, D. W. Carr, and M. Hunzicker-Dunn Neuronal Microtubule-associated Protein 2D Is a Dual A-kinase Anchoring Protein Expressed in Rat Ovarian Granulosa Cells J. Biol. Chem., June 25, 2004; 279(26): 27621 - 27632. [Abstract] [Full Text] [PDF]

				Y. Kalma, I. Granot, D. Galiani, A. Barash, and N. Dekel Luteinizing Hormone-Induced Connexin 43 Down-Regulation: Inhibition of Translation Endocrinology, April 1, 2004; 145(4): 1617 - 1624. [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]

				T. Hirakawa and M. Ascoli The Lutropin/Choriogonadotropin Receptor-Induced Phosphorylation of the Extracellular Signal-Regulated Kinases in Leydig Cells Is Mediated by a Protein Kinase A-Dependent Activation of Ras Mol. Endocrinol., November 1, 2003; 17(11): 2189 - 2200. [Abstract] [Full Text] [PDF]

				S. Dabizzi, I. Noci, P. Borri, E. Borrani, M. Giachi, M. Balzi, G. L. Taddei, M. Marchionni, G. F. Scarselli, and A. Arcangeli Luteinizing Hormone Increases Human Endometrial Cancer Cells Invasiveness through Activation of Protein Kinase A Cancer Res., July 15, 2003; 63(14): 4281 - 4286. [Abstract] [Full Text] [PDF]

				D. L. Russell, K. M. H. Doyle, I. Gonzales-Robayna, C. Pipaon, and J. S. Richards Egr-1 Induction in Rat Granulosa Cells by Follicle-Stimulating Hormone and Luteinizing Hormone: Combinatorial Regulation By Transcription Factors Cyclic Adenosine 3',5'-Monophosphate Regulatory Element Binding Protein, Serum Response Factor, Sp1, and Early Growth Response Factor-1 Mol. Endocrinol., April 1, 2003; 17(4): 520 - 533. [Abstract] [Full Text] [PDF]