This Article Full Text Full Text (PDF) 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 Ramírez, J. L. Articles by Gracia-Navarro, F. Search for Related Content PubMed PubMed Citation Articles by Ramírez, J. L. Articles by Gracia-Navarro, F.

Growth Hormone (GH)-Releasing Factor Differentially Activates Cyclic Adenosine 3',5'-Monophosphate- and Inositol Phosphate-Dependent Pathways to Stimulate GH Release in Two Porcine Somatotrope Subpopulations¹

Department of Cell Biology, University of Córdoba (J.L.R., J.P.C., R.T., A.J.M.-F., S.G.-N., F.G.-N.), 14004 Córdoba, Spain; and the Department of Cell Biology and Anatomy, Medical University of South Carolina (L.S.F.), Charleston, South Carolina 29425

Address all correspondence and requests for reprints to: Dr. F. Gracia-Navarro, Department of Cell Biology, Faculty of Sciences, Avda. San Alberto Magno s/n, University of Córdoba, 14004 Córdoba, Spain. E-mail: bc1grnaf{at}uco.es

Somatotropes comprise two morphologically and functionally distinct subpopulations of low (LD) and high (HD) density cells. We recently reported that GRF induces different patterns of increase in the cytosolic free Ca²⁺ concentration in single porcine LD and HD somatotropes, which for LD cells required not only Ca²⁺ influx but also intracellular Ca²⁺ mobilization. This suggested that GRF may activate multiple signaling pathways in pig LD and HD somatotropes to stimulate GH secretion. To address this question, we first assessed the direct GRF effect on second messenger activation in cultures of LD and HD cells by measuring cAMP levels and [³H]myo-inositol incorporation. Secondly, to determine the relative importance of cAMP- and inositol phosphate (IP)-dependent pathways, and of intra- and extracellular Ca²⁺, GRF-induced GH release from cultured LD and HD somatotropes was measured in the presence of specific blockers. GRF increased cAMP levels in both subpopulations, whereas it only augmented IP turnover in LD cells. Accordingly, adenylate cyclase inhibition by MDL-12,330A abolished GRF-stimulated GH release in both subpopulations, whereas phospholipase C inhibition by U-73122 only reduced this effect partially in LD cells. Likewise, blockade of Ca²⁺ influx with Cl₂Co reduced GRF-stimulated GH secretion in both LD and HD somatotropes, whereas depletion of thapsigargin-sensitive intracellular Ca²⁺ stores only decreased the secretory response to GRF in LD cells. These results demonstrate that GRF specifically and differentially activates multiple signaling pathways in two somatotrope subpopulations to stimulate GH release. Thus, although the prevailing signaling cascade employed by GRF in both subpopulations is adenylate cyclase/cAMP/extracellular Ca²⁺, the peptide also requires activation of the phospholipase C/IP/intracellular Ca²⁺ pathway to exert its full effect in porcine LD somatotropes.

This article has been cited by other articles:

				F. Rodriguez-Pacheco, R. Vazquez-Martinez, A. J. Martinez-Fuentes, M. R. Pulido, M. D. Gahete, H. Vaudry, F. Gracia-Navarro, C. Dieguez, J. P. Castano, and M. M. Malagon Resistin Regulates Pituitary Somatotrope Cell Function through the Activation of Multiple Signaling Pathways Endocrinology, October 1, 2009; 150(10): 4643 - 4652. [Abstract] [Full Text] [PDF]

				R. D. Kineman and R. M. Luque Evidence that Ghrelin Is as Potent as Growth Hormone (GH)-Releasing Hormone (GHRH) in Releasing GH from Primary Pituitary Cell Cultures of a Nonhuman Primate (Papio anubis), Acting through Intracellular Signaling Pathways Distinct from GHRH Endocrinology, September 1, 2007; 148(9): 4440 - 4449. [Abstract] [Full Text] [PDF]

				J. Rotllant, P. M. Guerreiro, L. Anjos, B. Redruello, A. V. M. Canario, and D. M. Power Stimulation of Cortisol Release by the N Terminus of Teleost Parathyroid Hormone-Related Protein in Interrenal Cells in Vitro Endocrinology, January 1, 2005; 146(1): 71 - 76. [Abstract] [Full Text] [PDF]

				R. M. Luque, R. D. Kineman, S. Park, X.-D. Peng, F. Gracia-Navarro, J. P. Castano, and M. M. Malagon Homologous and Heterologous Regulation of Pituitary Receptors for Ghrelin and Growth Hormone-Releasing Hormone Endocrinology, July 1, 2004; 145(7): 3182 - 3189. [Abstract] [Full Text] [PDF]

				M. M. Malagon, R. M. Luque, E. Ruiz-Guerrero, F. Rodriguez-Pacheco, S. Garcia-Navarro, F. F. Casanueva, F. Gracia-Navarro, and J. P. Castano Intracellular Signaling Mechanisms Mediating Ghrelin-Stimulated Growth Hormone Release in Somatotropes Endocrinology, December 1, 2003; 144(12): 5372 - 5380. [Abstract] [Full Text] [PDF]

				K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family Pharmacol. Rev., March 1, 2003; 55(1): 167 - 194. [Abstract] [Full Text] [PDF]

				J. L. Ramirez, F. Gracia-Navarro, S. Garcia-Navarro, R. Torronteras, M. M. Malagon, and J. P. Castano Somatostatin Stimulates GH Secretion in Two Porcine Somatotrope Subpopulations through a cAMP-Dependent Pathway Endocrinology, March 1, 2002; 143(3): 889 - 897. [Abstract] [Full Text] [PDF]

				K. Venkatesh, G. Siddhartha, R. Joshi, S. Patel, and G. Hasan Interactions Between the Inositol 1,4,5-Trisphosphate and Cyclic AMP Signaling Pathways Regulate Larval Molting in Drosophila Genetics, May 1, 2001; 158(1): 309 - 318. [Abstract] [Full Text]