| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Center for Endocrinological Oncology, Department of Endocrinology (P.L., R.M.M., M.M.M., D.D., M.M.), and Department of Medical Pharmacology (M.P.), University of Milano, 20133 Milano, Italy
Address all correspondence and requests for reprints to: Dr. P. Limonta, Center for Endocrinological Oncology, Department of Endocrinology, Via Balzaretti 9, 20133 Milano, Italy. E-mail: limonta{at}mailserver.unimi.it
Evidence has accumulated indicating that LHRH might behave as an
autocrine/paracrine growth inhibitory factor in some peripheral tumors.
However, LHRH receptors in tumor cells have not been fully
characterized, so far. The present experiments were performed to
analyze: 1) the messenger RNA expression; 2) the molecular size;
and 3) the signal transduction pathway of LHRH receptors in prostate
cancer. For these studies, the human androgen-dependent LNCaP and
androgen-independent DU 145 prostate cancer cell lines were used.
1) By RT-PCR, a complementary DNA product, which hybridized with
a 32P-labeled oligonucleotide probe specific for the
pituitary LHRH receptor complementary DNA, was found both in LNCaP and
in DU 145 cells. 2) Western blot analysis, using a monoclonal antibody
raised against the human pituitary LHRH receptor, revealed the presence
of a protein band of approximately 64 kDa (corresponding to the
molecular mass of the pituitary receptor) in both cell lines. 3) In
LNCaP and DU 145 cells, pertussis toxin completely abrogated the
antiproliferative action of a LHRH agonist (LHRH-A). Moreover, LHRH-A
substantially antagonized the pertussis toxin-catalyzed
ADP-ribosylation of a G
i protein. Finally, LHRH-A
significantly counteracted the forskolin-induced increase of
intracellular cAMP levels in both cell lines. These data demonstrate
that the LHRH receptor, which is present in prostate cancer cells,
independently of whether they are androgen-dependent or not,
corresponds to the pituitary receptor, in terms of messenger RNA
expression and protein molecular size. However, at variance with the
receptor of the gonadotrophs, prostate cancer LHRH receptor seems
to be coupled to the Gi protein-cAMP signal transduction
pathway, rather than to the Gq/11-phospholipase C
signaling system. This might be responsible for the different actions
of LHRH in anterior pituitary and in prostate cancer.
This article has been cited by other articles:
 |
|
 |
|
  R. Lopez de Maturana, A. J. Pawson, Z.-L. Lu, L. Davidson, S. Maudsley, K. Morgan, S. P. Langdon, and R. P. Millar Gonadotropin-Releasing Hormone Analog Structural Determinants of Selectivity for Inhibition of Cell Growth: Support for the Concept of Ligand-Induced Selective Signaling Mol. Endocrinol., July 1, 2008; 22(7): 1711 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Walters, I. N. Wegorzewska, Y.-P. Chin, M. G. Parikh, and T. J. Wu Luteinizing Hormone-Releasing Hormone I (LHRH-I) and Its Metabolite in Peripheral Tissues Experimental Biology and Medicine, February 1, 2008; 233(2): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Darby, J Stockley, M M Khan, C N Robson, H Y Leung, and V J Gnanapragasam Expression of GnRH type II is regulated by the androgen receptor in prostate cancer Endocr. Relat. Cancer, September 1, 2007; 14(3): 613 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C.K. Leung and J.-H. Choi Endocrine signaling in ovarian surface epithelium and cancer Hum. Reprod. Update, March 1, 2007; 13(2): 143 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Princivalle, P. Broqua, R. White, J. Meyer, G. Mayer, L. Elliott, K. Bjarnason, R. Haigh, and C. Yea Rapid Suppression of Plasma Testosterone Levels and Tumor Growth in the Dunning Rat Model Treated with Degarelix, a New Gonadotropin-Releasing Hormone Antagonist J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1113 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Baldwin, I. N. Wegorzewska, M. Flora, and T. J. Wu Regulation of Type II Luteinizing Hormone-Releasing Hormone (LHRH-II) Gene Expression by the Processed Peptide of LHRH-I, LHRH-(1-5) in Endometrial Cells Experimental Biology and Medicine, January 1, 2007; 232(1): 146 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, C. B. Gilks, N. Auersperg, and P. C. K. Leung Immunolocalization of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Type I GnRH Receptor during Follicular Development in the Human Ovary J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4562 - 4570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Maiti, D. Y. Oh, J. S. Moon, S. Acharjee, J. H. Li, D. G. Bai, H.-S. Park, K. Lee, Y. C. Lee, N. C. Jung, et al. Differential Effects of Gonadotropin-Releasing Hormone (GnRH)-I and GnRH-II on Prostate Cancer Cell Signaling and Death J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4287 - 4298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chen, S. Yoshida, N. Ohara, H. Matsuo, M. Morizane, and T. Maruo Gonadotropin-Releasing Hormone Antagonist Cetrorelix Down-Regulates Proliferating Cell Nuclear Antigen and Epidermal Growth Factor Expression and Up-Regulates Apoptosis in Association with Enhanced Poly(Adenosine 5'-Diphosphate-Ribose) Polymerase Expression in Cultured Human Leiomyoma Cells J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 884 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Maudsley, L. Davidson, A. J. Pawson, R. Chan, R. L. de Maturana, and R. P. Millar Gonadotropin-Releasing Hormone (GnRH) Antagonists Promote Proapoptotic Signaling in Peripheral Reproductive Tumor Cells by Activating a G{alpha}i-Coupling State of the Type I GnRH Receptor Cancer Res., October 15, 2004; 64(20): 7533 - 7544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kraus, G. Levy, T. Hanoch, Z. Naor, and R. Seger Gonadotropin-Releasing Hormone Induces Apoptosis of Prostate Cancer Cells: Role of c-Jun NH2-Terminal Kinase, Protein Kinase B, and Extracellular Signal-Regulated Kinase Pathways Cancer Res., August 15, 2004; 64(16): 5736 - 5744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Millar, Z.-L. Lu, A. J. Pawson, C. A. Flanagan, K. Morgan, and S. R. Maudsley Gonadotropin-Releasing Hormone Receptors Endocr. Rev., April 1, 2004; 25(2): 235 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Romanelli, T. Barni, M. Maggi, M. Luconi, P. Failli, A. Pezzatini, E. Pelo, F. Torricelli, C. Crescioli, P. Ferruzzi, et al. Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons: AN AUTOCRINE GnRH LOOP UNDERLIES NEURONAL MIGRATION J. Biol. Chem., January 2, 2004; 279(1): 117 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chamson-Reig, E. M. Sorianello, P. N. Catalano, M. O. Fernandez, O. P. Pignataro, C. Libertun, and V. A. R. Lux-Lantos Gonadotropin-Releasing Hormone Signaling Pathways in an Experimental Ovarian Tumor Endocrinology, July 1, 2003; 144(7): 2957 - 2966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Morgan, D. Conklin, A. J. Pawson, R. Sellar, T. R. Ott, and R. P. Millar A Transcriptionally Active Human Type II Gonadotropin-Releasing Hormone Receptor Gene Homolog Overlaps Two Genes in the Antisense Orientation on Chromosome 1q.12 Endocrinology, February 1, 2003; 144(2): 423 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Moretti, M. Montagnani Marelli, J. C. Van Groeninghen, and P. Limonta Locally Expressed LHRH Receptors Mediate the Oncostatic and Antimetastatic Activity of LHRH Agonists on Melanoma Cells J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3791 - 3797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wells, J. C. S. Souto, J. Solava, J. Kassis, K. J. Bailey, and T. Turner Luteinizing Hormone-releasing Hormone Agonist Limits DU-145 Prostate Cancer Growth by Attenuating Epidermal Growth Factor Receptor Signaling Clin. Cancer Res., April 1, 2002; 8(4): 1251 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Straub, M. Muller, H. Krause, M. Schrader, C. Goessl, R. Heicappell, and K. Miller Increased Incidence of Luteinizing Hormone-releasing Hormone Receptor Gene Messenger RNA Expression in Hormone-refractory Human Prostate Cancers Clin. Cancer Res., August 1, 2001; 7(8): 2340 - 2343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Grundker, P. Volker, and G. Emons Antiproliferative Signaling of Luteinizing Hormone-Releasing Hormone in Human Endometrial and Ovarian Cancer Cells through G Protein {{alpha}}I-Mediated Activation of Phosphotyrosine Phosphatase Endocrinology, June 1, 2001; 142(6): 2369 - 2380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Auersperg, A. S. T. Wong, K.-C. Choi, S. K. Kang, and P. C. K. Leung Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology Endocr. Rev., April 1, 2001; 22(2): 255 - 288. [Abstract] [Full Text]
|
|
|
|
|
|
L. Z. Krsmanovic, N. Mores, C. E. Navarro, M. Tomic, and K. J. Catt Regulation of Ca2+-Sensitive Adenylyl Cyclase in Gonadotropin-Releasing Hormone Neurons Mol. Endocrinol., March 1, 2001; 15(3): 429 - 440. [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]
|
|
|
|
|
|
K. W. Cheng, P. S. Nathwani, and P. C. K. Leung Regulation of Human Gonadotropin-Releasing Hormone Receptor Gene Expression in Placental Cells Endocrinology, July 1, 2000; 141(7): 2340 - 2349. [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 |
