| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology, Vol 134, 315-323, Copyright © 1994 by Endocrine Society
ARTICLES |
E Schomerus, A Poch, R Bunting, WT Mason and CA McArdle
Institute for Hormone and Fertility Research, University of Hamburg, Germany.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is thought to play a hypophysiotropic role, but little is known of the identity of PACAP-stimulated cells in the pituitary, the nature of the PACAP receptors on specific cell types, and the effector systems for these receptors. Here we describe the effects of PACAP in alpha T3-1 cells, a gonadotrope-derived cell line. In these cells, PACAP38 causes concentration-dependent increases in cAMP accumulation (EC50, 3 nM), [3H]inositol phosphate ([3H]IP) production (EC50, 20 nM), and the cytosolic Ca2+ concentration. The Ca2+ response is biphasic and is sustained only in Ca(2+)-containing medium. Intact alpha T3-1 cells possess a single class of [125I]PACAP27-binding sites (Kd, 3.3 nM; binding capacity, 35 fmol/10(6) cells). The rank orders of potencies for stimulation of cAMP and [3H]IP production and for inhibition of [125I] PACAP27 binding by three related peptides are identical (PACAP38 = PACAP27 > > vasoactive intestinal peptide). In addition to stimulation of LH release from primary cultures of rat pituitary cells and [3H] IP accumulation in alpha T3-1 cells, PACAP38 synergizes with low GnRH concentrations in the production of these effects. Moreover, long term exposure to PACAP38 stimulates [3H]thymidine incorporation and increases steady state levels of the gonadotropin alpha-subunit in alpha T3-1 cells. We conclude that alpha T3-1 cells possess type I PACAP receptors which mediate the observed effector system responses, and demonstration of the effects of PACAP on this gonadotrope-derived cell line provides further evidence that gonadotropes are direct targets for PACAP action. The data imply that stimulation of phospholipase-C by PACAP is responsible (at least in part) for the observed increase in cytosolic Ca2+, which, in turn, probably mediates the effects of PACAP on LH release. We suggest, however, that in gonadotropes, the effects of PACAP on cell replication and gonadotropin synthesis may prove more important than the peptide's modest effects on LH release.
This article has been cited by other articles:
 |
|
 |
|
  S. Lariviere, G. Garrel-Lazayres, V. Simon, N. Shintani, A. Baba, R. Counis, and J. Cohen-Tannoudji Gonadotropin-Releasing Hormone Inhibits Pituitary Adenylyl Cyclase-Activating Polypeptide Coupling to 3',5'-Cyclic Adenosine-5'-Monophosphate Pathway in L{beta}T2 Gonadotrope Cells through Novel Protein Kinase C Isoforms and Phosphorylation of Pituitary Adenylyl Cyclase-Activating Polypeptide Type I Receptor Endocrinology, December 1, 2008; 149(12): 6389 - 6398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Harada, H. Kanasaki, S. Mutiara, A. Oride, and K. Miyazaki Cyclic Adenosine 3',5'Monophosphate/Protein Kinase A and Mitogen-Activated Protein Kinase 3/1 Pathways Are Involved in Adenylate Cyclase-Activating Polypeptide 1-Induced Common Alpha-Glycoprotein Subunit Gene (Cga) Expression in Mouse Pituitary Gonadotroph LbetaT2 Cells Biol Reprod, October 1, 2007; 77(4): 707 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chi-Wei, S.-L. Chang, and C.-F. Weng Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Regulates the Expression of PACAP in Cultured Tilapia Astrocytes Experimental Biology and Medicine, February 1, 2007; 232(2): 262 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Moore Jr, L. L. Burger, A. C. Dalkin, and S. J. Winters Pituitary Adenylate Cyclase Activating Polypeptide Messenger RNA in the Paraventricular Nucleus and Anterior Pituitary During the Rat Estrous Cycle Biol Reprod, September 1, 2005; 73(3): 491 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Fowkes, M. Desclozeaux, M. V. Patel, S. J. B. Aylwin, P. King, H. A. Ingraham, and J. M. Burrin Steroidogenic Factor-1 and The Gonadotrope-Specific Element Enhance Basal and Pituitary Adenylate Cyclase-Activating Polypeptide-Stimulated Transcription of the Human Glycoprotein Hormone {alpha}-Subunit Gene in Gonadotropes Mol. Endocrinol., November 1, 2003; 17(11): 2177 - 2188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, A. O. L. Wong, and W. Ge Cloning, Regulation of Messenger Ribonucleic Acid Expression, and Function of a New Isoform of Pituitary Adenylate Cyclase-Activating Polypeptide in the Zebrafish Ovary Endocrinology, November 1, 2003; 144(11): 4799 - 4810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Garrel, A. Lozach, L. K. Bachir, J.-N. Laverriere, and R. Counis Pituitary Adenylate Cyclase-activating Polypeptide Stimulates Nitric-oxide Synthase Type I Expression and Potentiates the cGMP Response to Gonadotropin-releasing Hormone of Rat Pituitary Gonadotrophs J. Biol. Chem., November 22, 2002; 277(48): 46391 - 46401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Schreihofer, E. M. Resnick, V. Y. Lin, and M. A. Shupnik Ligand-Independent Activation of Pituitary ER: Dependence on PKA-Stimulated Pathways Endocrinology, August 1, 2001; 142(8): 3361 - 3368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. McCulloch, E. M. Lutz, M. S. Johnson, D. N. Robertson, C. J. MacKenzie, P. J. Holland, and R. Mitchell ADP-Ribosylation Factor-Dependent Phospholipase D Activation by VPAC Receptors and a PAC1 Receptor Splice Variant Mol. Pharmacol., June 1, 2001; 59(6): 1523 - 1532. [Abstract] [Full Text]
|
|
|
|
|
|
S. K. Kang, C.-J. Tai, P. S. Nathwani, K.-C. Choi, and P. C. K. Leung Stimulation of Mitogen-Activated Protein Kinase by Gonadotropin-Releasing Hormone in Human Granulosa-Luteal Cells Endocrinology, February 1, 2001; 142(2): 671 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Sherwood, S. L. Krueckl, and J. E. McRory The Origin and Function of the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)/Glucagon Superfamily Endocr. Rev., December 1, 2000; 21(6): 619 - 670. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. Vaudry, B. J. Gonzalez, M. Basille, L. Yon, A. Fournier, and H. Vaudry Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions Pharmacol. Rev., June 1, 2000; 52(2): 269 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Grosse, A. Schmid, T. Schoneberg, A. Herrlich, P. Muhn, G. Schultz, and T. Gudermann Gonadotropin-releasing Hormone Receptor Initiates Multiple Signaling Pathways by Exclusively Coupling to Gq/11 Proteins J. Biol. Chem., March 24, 2000; 275(13): 9193 - 9200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-b. Han and P. M. Conn The Role of Protein Kinases A and C Pathways in the Regulation of Mitogen-Activated Protein Kinase Activation in Response to Gonadotropin-Releasing Hormone Receptor Activation Endocrinology, May 1, 1999; 140(5): 2241 - 2251. [Abstract] [Full Text]
|
|
|
|
|
|
J. J. Evans Modulation of Gonadotropin Levels by Peptides Acting at the Anterior Pituitary Gland Endocr. Rev., February 1, 1999; 20(1): 46 - 67. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. D. A. Kopp, C. Schomerus, F. Dehghani, H.-W. Korf, and H. Meissl Pituitary Adenylate Cyclase-Activating Polypeptide and Melatonin in the Suprachiasmatic Nucleus: Effects on the Calcium Signal Transduction Cascade J. Neurosci., January 1, 1999; 19(1): 206 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Burrin, S. J. B. Aylwin, J. G. Holdstock, and U. Sahye Mechanism of Action of Pituitary Adenylate Cyclase-Activating Polypeptide on Human Glycoprotein Hormone {alpha}-Subunit Transcription in {alpha}T3-1 Gonadotropes Endocrinology, April 1, 1998; 139(4): 1731 - 1737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hezareh, W. Schlegel, and S. R. Rawlings Stimulation of Ca2+ influx in alpha T3-1 gonadotrophs via the cAMP/PKA signaling system Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E850 - E858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Winters, A. C. Dalkin, and T. Tsujii Evidence That Pituitary Adenylate Cyclase Activating Polypeptide Suppresses Follicle-Stimulating Hormone-{beta} Messenger Ribonucleic Acid Levels by Stimulating Follistatin Gene Transcription Endocrinology, October 1, 1997; 138(10): 4324 - 4329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Garrel, C. A. McArdle, B. A. Hemmings, and R. Counis Gonadotropin-Releasing Hormone and Pituitary Adenylate Cyclase-Activating Polypeptide Affect Levels of Cyclic Adenosine 3',5'-Monophosphate-Dependent Protein Kinase A (PKA) Subunits in the Clonal Gonadotrope {alpha}T3-1 Cells: Evidence for Cross-Talk between PKA and Protein Kinase C Pathways Endocrinology, June 1, 1997; 138(6): 2259 - 2266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Chatterjee, X. Liu, R. L. Davisson, and R. A. Fisher Genomic Organization of the Rat Pituitary Adenylate Cyclase-activating Polypeptide Receptor Gene. ALTERNATIVE SPLICING WITHIN THE 5prime -UNTRANSLATED REGION J. Biol. Chem., May 2, 1997; 272(18): 12122 - 12131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Chatterjee, R. V. Sharma, and R. A. Fisher Molecular Cloning of a Novel Variant of the Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Receptor That Stimulates Calcium Influx by Activation of L-type Calcium Channels J. Biol. Chem., December 13, 1996; 271(50): 32226 - 32232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. McArdle, G. B. Willars, R. C. Fowkes, S. R. Nahorski, J. S. Davidson, and W. Forrest-Owen Desensitization of Gonadotropin-releasing Hormone Action in alpha T3-1 Cells Due to Uncoupling of Inositol 1,4,5-Trisphosphate Generation and Ca2+ Mobilization J. Biol. Chem., September 27, 1996; 271(39): 23711 - 23717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Pisegna and S. A. Wank Cloning and Characterization of the Signal Transduction of Four Splice Variants of the Human Pituitary Adenylate Cyclase Activating Polypeptide Receptor. EVIDENCE FOR DUAL COUPLING TO ADENYLATE CYCLASE AND PHOSPHOLIPASE C J. Biol. Chem., July 19, 1996; 271(29): 17267 - 17274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Pincas, J.-N. Laverriere, and R. Counis Pituitary Adenylate Cyclase-activating Polypeptide and Cyclic Adenosine 3',5'-Monophosphate Stimulate the Promoter Activity of the Rat Gonadotropin-releasing Hormone Receptor Gene via a Bipartite Response Element in Gonadotrope-derived Cells J. Biol. Chem., June 22, 2001; 276(26): 23562 - 23571. [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 |
