| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Contraceptive Development Branch, Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20892
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute La Jolla, California 92037
Correspondence: Address requests for reprints to: Dr. Marvin J. Karten, Contraceptive Development Branch, Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Abstract
Introduction: ON JUNE 24, 1971, Andrew V. Schally announced the determination of the primary structure of porcine GnRH at The Endocrine Society Meeting in San Francisco. This announcement was followed by publications by Matsuo et al. (1, 2) and Baba et al. (3) on the proposed amino acid sequence for porcine GnRH and its synthesis and by Burgus et al. (4) who characterized ovine GnRH and found the sequence to be identical with that of porcine GnRH. The physiological and therapeutic importance attributed to the discovery of the new substance was greatly increased by the prospect of the design of potent and long acting GnRH agonists and antagonists. Since that time more than 2000 analogs of GnRH have been synthesized. The impact of research of GnRH and its analogs on clinical medicine recently led Ziporyn (5) to note, "There's almost no subspecialty of medicine that will be left untouched by the [research] advances associated with LHRH or its analogs." It is the intent of this article to provide a historical review of the major, and some minor, aspects of the chemical development of GnRH agonists and antagonists up to the present state of development (July 1, 1985). The synthetic chemical efforts have been devoted largely to increasing the affinity of the peptides to the GnRH receptor and their resistance to degradation or elimination in in vivo systems, characteristics which, for the GnRH analogs, are generally interrelated.
This article has been cited by other articles:
 |
|
 |
|
  E. M Delemarre, B. Felius, and H. A Delemarre-van de Waal Inducing puberty Eur. J. Endocrinol., December 1, 2008; 159(suppl_1): S9 - S15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 C. Metallinou, B. Asimakopoulos, A. Schroer, and N. Nikolettos Gonadotropin-Releasing Hormone in the Ovary Reproductive Sciences, December 1, 2007; 14(8): 737 - 749. [Abstract] [PDF]
|
|
|
|
 |
|
 L. W.T. Cheung, P. C.K. Leung, and A. S.T. Wong Gonadotropin-Releasing Hormone Promotes Ovarian Cancer Cell Invasiveness through c-Jun NH2-Terminal Kinase-Mediated Activation of Matrix Metalloproteinase (MMP)-2 and MMP-9. Cancer Res., November 15, 2006; 66(22): 10902 - 10910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Leanos-Miranda, A. Ulloa-Aguirre, L. A Cervini, J. A. Janovick, J. Rivier, and P M. Conn Identification of new gonadotrophin-releasing hormone partial agonists. J. Endocrinol., June 1, 2006; 189(3): 509 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Ratcliffe, H. M. Fraser, R. Sellar, J. Rivier, and R. P. Millar Bifunctional Gonadotropin-Releasing Hormone Antagonist-Progesterone Analogs with Increased Efficacy and Duration of Action Endocrinology, January 1, 2006; 147(1): 571 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Barran, R. W. Roeske, A. J. Pawson, R. Sellar, M. T. Bowers, K. Morgan, Z.-L. Lu, M. Tsuda, T. Kusakabe, and R. P. Millar Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity J. Biol. Chem., November 18, 2005; 280(46): 38569 - 38575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G S Harrison, M E Wierman, T M Nett, and L M Glode Gonadotropin-releasing hormone and its receptor in normal and malignant cells Endocr. Relat. Cancer, December 1, 2004; 11(4): 725 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Baker, M. A. Wild, M. M. Connor, H. B. Ravivarapu, R. L. Dunn, and T. M. Nett GONADOTROPIN-RELEASING HORMONE AGONIST: A NEW APPROACH TO REVERSIBLE CONTRACEPTION IN FEMALE DEER J. Wildl. Dis., October 1, 2004; 40(4): 713 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Reinhart, Q. Xie, X.-J. Liu, Y.-F. Zhu, J. Fan, C. Chen, and R. S. Struthers Species Selectivity of Nonpeptide Antagonists of the Gonadotropinreleasing Hormone Receptor Is Determined by Residues in Extracellular Loops II and III and the Amino Terminus J. Biol. Chem., August 13, 2004; 279(33): 34115 - 34122. [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]
|
|
|
|
|
|
L. Qi, T. M. Nett, M. C. Allen, X. Sha, G. S. Harrison, B. A. Frederick, E. D. Crawford, and L. M. Glode Binding and Cytotoxicity of Conjugated and Recombinant Fusion Proteins Targeted to the Gonadotropin-Releasing Hormone Receptor Cancer Res., March 15, 2004; 64(6): 2090 - 2095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. C. Miles, A. C. Hanyaloglu, J. R. Dromey, K. D. G. Pfleger, and K. A. Eidne Gonadotropin-Releasing Hormone Receptor-Mediated Growth Suppression of Immortalized L{beta}T2 Gonadotrope and Stable HEK293 Cell Lines Endocrinology, January 1, 2004; 145(1): 194 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-H. Yang, M. Wieczorck, M. C. Allen, and T. M. Nett Cytotoxic Activity of Gonadotropin-Releasing Hormone (GnRH)-Pokeweed Antiviral Protein Conjugates in Cell Lines Expressing GnRH Receptors Endocrinology, April 1, 2003; 144(4): 1456 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. G. Pfleger, J. Bogerd, and R. P. Millar Conformational Constraint of Mammalian, Chicken, and Salmon GnRHs, But Not GnRH II, Enhances Binding at Mammalian and Nonmammalian Receptors: Evidence for Preconfiguration of GnRH II Mol. Endocrinol., September 1, 2002; 16(9): 2155 - 2162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Herbst, B. D. Anawalt, J. K. Amory, and W. J. Bremner Acyline: The First Study in Humans of a Potent, New Gonadotropin-Releasing Hormone Antagonist J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3215 - 3220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Grove-Strawser, S. A. Sower, P. M. Ronsheim, J. B. Connolly, C. G. Bourn, and B. S. Rubin Guinea Pig GnRH: Localization and Physiological Activity Reveal That It, Not Mammalian GnRH, Is the Major Neuroendocrine Form in Guinea Pigs Endocrinology, May 1, 2002; 143(5): 1602 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Fromme, A. A. Katz, R. W. Roeske, R. P. Millar, and C. A. Flanagan Role of Aspartate7.32(302) of the Human Gonadotropin-Releasing Hormone Receptor in Stabilizing a High-Affinity Ligand Conformation Mol. Pharmacol., December 1, 2001; 60(6): 1280 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Schwartz Perspective: Reproductive Endocrinology and Human Health in the 20th Century--A Personal Retrospective Endocrinology, June 1, 2001; 142(6): 2163 - 2166. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ortmann, J.M. Weiss, and K. Diedrich Embryo implantation and GnRH antagonists: Ovarian actions of GnRH antagonists Hum. Reprod., April 1, 2001; 16(4): 608 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Hoffmann, T. t. Laak, R. Kühne, H. Reiländer, and T. Beckers Residues within Transmembrane Helices 2 and 5 of the Human Gonadotropin-Releasing Hormone Receptor Contribute to Agonist and Antagonist Binding Mol. Endocrinol., July 1, 2000; 14(7): 1099 - 1115. [Abstract] [Full Text]
|
|
|
|
|
|
E. R. Hernandez Embryo implantation and GnRH antagonists: Embryo implantation: the Rubicon for GnRH antagonists Hum. Reprod., June 1, 2000; 15(6): 1211 - 1216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yahalom, Y. Koch, N. Ben-Aroya, and M. Fridkin Hexapeptide and Cyclic Pentapeptide Endothelin Antagonists Directly Activate Pituitary Gonadotropin-Releasing Hormone Receptors Mol. Pharmacol., April 1, 2000; 57(4): 718 - 724. [Abstract] [Full Text]
|
|
|
|
|
|
S. Chauvin, A. Bérault, Y. Lerrant, M. Hibert, and R. Counis Functional Importance of Transmembrane Helix 6 Trp279 and Exoloop 3 Val299 of Rat Gonadotropin-Releasing Hormone Receptor Mol. Pharmacol., March 1, 2000; 57(3): 625 - 633. [Abstract] [Full Text]
|
|
|
|
|
|
J. L. Sharpless, J. G. Supko, K. A. Martin, and J. E. Hall Disappearance of Endogenous Luteinizing Hormone Is Prolonged in Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 688 - 694. [Abstract] [Full Text]
|
|
|
|
|
|
C. A. Flanagan, B. J. Fromme, J. S. Davidson, and R. P. Millar A High Affinity Gonadotropin-Releasing Hormone (GnRH) Tracer, Radioiodinated at Position 6, Facilitates Analysis of Mutant GnRH Receptors Endocrinology, October 1, 1998; 139(10): 4115 - 4119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jimenez-Linan, B. S. Rubin, and J. C. King Examination of Guinea Pig Luteinizing Hormone-Releasing Hormone Gene Reveals a Unique Decapeptide and Existence of Two Transcripts in the Brain Endocrinology, October 1, 1997; 138(10): 4123 - 4130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. F. Cook and K. A. Eidne An Intramolecular Disulfide Bond between Conserved Extracellular Cysteines in the Gonadotropin-Releasing Hormone Receptor Is Essential for Binding and Activation Endocrinology, July 1, 1997; 138(7): 2800 - 2806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Sealfon, H. Weinstein, and R. P. Millar Molecular Mechanisms of Ligand Interaction with the Gonadotropin-Releasing Hormone Receptor Endocr. Rev., April 1, 1997; 18(2): 180 - 205. [Abstract] [Full Text]
|
|
|
|
|
|
J. S. Davidson, C. A. McArdle, P. Davies, R. Elario, C. A. Flanagan, and R. P. Millar Asn102 of the Gonadotropin-releasing Hormone Receptor Is a Critical Determinant of Potency for Agonists Containing C-terminal Glycinamide J. Biol. Chem., June 28, 1996; 271(26): 15510 - 15514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhou, V. Rodic, S. Kitanovic, C. A. Flanagan, L. Chi, H. Weinstein, S. Maayani, R. P. Millar, and S. C. Sealfon A Locus of the Gonadotropin-releasing Hormone Receptor That Differentiates Agonist and Antagonist Binding Sites J. Biol. Chem., August 11, 1995; 270(32): 18853 - 18857. [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 |
