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Department of Endocrinology and Reproduction (A.P.N.T.), Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands; and Department of Physiology (I.T.H.), University of Turku, 20520 Turku, Finland
The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHß subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases.
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G. Meduri, P. Touraine, I. Beau, O. Lahuna, A. Desroches, M. C. Vacher-Lavenu, F. Kuttenn, and M. Misrahi Delayed Puberty and Primary Amenorrhea Associated with a Novel Mutation of the Human Follicle-Stimulating Hormone Receptor: Clinical, Histological, and Molecular Studies J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3491 - 3498. [Abstract] [Full Text] [PDF]
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A. Ulloa-Aguirre, C. Timossi, J. Barrios-de-Tomasi, A. Maldonado, and P. Nayudu Impact of Carbohydrate Heterogeneity in Function of Follicle-Stimulating Hormone: Studies Derived from in Vitro and in Vivo Models Biol Reprod, August 1, 2003; 69(2): 379 - 389. [Abstract] [Full Text] [PDF]
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K. Tajima, A. Dantes, Z. Yao, K. Sorokina, F. Kotsuji, R. Seger, and A. Amsterdam Down-Regulation of Steroidogenic Response to Gonadotropins in Human and Rat Preovulatory Granulosa Cells Involves Mitogen-Activated Protein Kinase Activation and Modulation of DAX-1 and Steroidogenic Factor-1 J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2288 - 2299. [Abstract] [Full Text] [PDF]
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N. C. Zachos, R. B. Billiar, E. D. Albrecht, and G. J. Pepe Developmental Regulation of Follicle-Stimulating Hormone Receptor Messenger RNA Expression in the Baboon Fetal Ovary Biol Reprod, May 1, 2003; 68(5): 1911 - 1917. [Abstract] [Full Text] [PDF]
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H. F. Vischer, J. C. M. Granneman, M. J. Noordam, S. Mosselman, and J. Bogerd Ligand Selectivity of Gonadotropin Receptors. ROLE OF THE beta -STRANDS OF EXTRACELLULAR LEUCINE-RICH REPEATS 3 AND 6 OF THE HUMAN LUTEINIZING HORMONE RECEPTOR J. Biol. Chem., April 25, 2003; 278(18): 15505 - 15513. [Abstract] [Full Text] [PDF]
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B. L. Powell, D. Piersma, M. E. Kevenaar, I. L. van Staveren, A. P. N. Themmen, B. J. Iacopetta, and E. M. J. J. Berns Luteinizing Hormone Signaling and Breast Cancer: Polymorphisms and Age of Onset J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1653 - 1657. [Abstract] [Full Text] [PDF]
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H. Shinozaki, V. Butnev, Y.-X. Tao, K. L. Ang, M. Conti, and D. L. Segaloff Desensitization of Gs-Coupled Receptor Signaling by Constitutively Active Mutants of the Human Lutropin/Choriogonadotropin Receptor J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1194 - 1204. [Abstract] [Full Text] [PDF]
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M. Haywood, J. Spaliviero, M. Jimemez, N. J. C. King, D. J. Handelsman, and C. M. Allan Sertoli and Germ Cell Development in Hypogonadal (hpg) Mice Expressing Transgenic Follicle-Stimulating Hormone Alone or in Combination with Testosterone Endocrinology, February 1, 2003; 144(2): 509 - 517. [Abstract] [Full Text] [PDF]
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L. A. Allen, J. C. Achermann, P. Pakarinen, T. J. Kotlar, I. T. Huhtaniemi, J. L. Jameson, T. D. Cheetham, and S. G. Ball A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics Hum. Reprod., February 1, 2003; 18(2): 251 - 256. [Abstract] [Full Text] [PDF]
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H.F. Vischer and J. Bogerd Cloning and Functional Characterization of a Gonadal Luteinizing Hormone Receptor Complementary DNA from the African Catfish (Clarias gariepinus) Biol Reprod, January 1, 2003; 68(1): 262 - 271. [Abstract] [Full Text] [PDF]
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R. A. Anderson and D. T. Baird Male Contraception Endocr. Rev., December 1, 2002; 23(6): 735 - 762. [Abstract] [Full Text] [PDF]
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M. Conti Specificity of the Cyclic Adenosine 3',5'-Monophosphate Signal in Granulosa Cell Function Biol Reprod, December 1, 2002; 67(6): 1653 - 1661. [Abstract] [Full Text] [PDF]
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P. Pakarinen, S. Kimura, F. El-Gehani, L. J. Pelliniemi, and I. Huhtaniemi Pituitary Hormones Are Not Required for Sexual Differentiation of Male Mice: Phenotype of the T/ebp/Nkx2.1 Null Mutant Mice Endocrinology, November 1, 2002; 143(11): 4477 - 4482. [Abstract] [Full Text] [PDF]
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T. Lamminen, M. Jiang, P. R. Manna, P. Pakarinen, H. Simonsen, R. J. Herrera, and I. Huhtaniemi Functional study of a recombinant form of human LH{beta}-subunit variant carrying the Gly102Ser mutation found in Asian populations Mol. Hum. Reprod., October 1, 2002; 8(10): 887 - 892. [Abstract] [Full Text] [PDF]
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S. B. Rulli, A. Kuorelahti, O. Karaer, L. J. Pelliniemi, M. Poutanen, and I. Huhtaniemi Reproductive Disturbances, Pituitary Lactotrope Adenomas, and Mammary Gland Tumors in Transgenic Female Mice Producing High Levels of Human Chorionic Gonadotropin Endocrinology, October 1, 2002; 143(10): 4084 - 4095. [Abstract] [Full Text] [PDF]
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K. H. Burns and M. M. Matzuk Minireview: Genetic Models for the Study of Gonadotropin Actions Endocrinology, August 1, 2002; 143(8): 2823 - 2835. [Abstract] [Full Text] [PDF]
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U. Pfeffer, D. Bisacchi, M. Morini, R. Benelli, S. Minghelli, A. Vacca, D. M. Noonan, and A. Albini Human Chorionic Gonadotropin Inhibits Kaposi's Sarcoma Associated Angiogenesis, Matrix Metalloprotease Activity, and Tumor Growth Endocrinology, August 1, 2002; 143(8): 3114 - 3121. [Abstract] [Full Text] [PDF]
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Y.-X. Tao, D. Mizrachi, and D. L. Segaloff Chimeras of the Rat and Human FSH Receptors (FSHRs) Identify Residues that Permit or Suppress Transmembrane 6 Mutation-Induced Constitutive Activation of the FSHR via Rearrangements of Hydrophobic Interactions Between Helices 6 and 7 Mol. Endocrinol., August 1, 2002; 16(8): 1881 - 1892. [Abstract] [Full Text] [PDF]
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S. Y. Hsu, K. Nakabayashi, and A. Bhalla Evolution of Glycoprotein Hormone Subunit Genes in Bilateral Metazoa: Identification of Two Novel Human Glycoprotein Hormone Subunit Family Genes, GPA2 and GPB5 Mol. Endocrinol., July 1, 2002; 16(7): 1538 - 1551. [Abstract] [Full Text] [PDF]
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C. Betterle, C. Dal Pra, F. Mantero, and R. Zanchetta Autoimmune Adrenal Insufficiency and Autoimmune Polyendocrine Syndromes: Autoantibodies, Autoantigens, and Their Applicability in Diagnosis and Disease Prediction Endocr. Rev., June 1, 2002; 23(3): 327 - 364. [Abstract] [Full Text] [PDF]
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J. C. Achermann, G. Ozisik, J. J. Meeks, and J. L. Jameson Genetic Causes of Human Reproductive Disease J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2447 - 2454. [Full Text] [PDF]
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J. W. M. Martens, S. Lumbroso, M. Verhoef-Post, V. Georget, A. Richter-Unruh, M. Szarras-Czapnik, T. E. Romer, H. G. Brunner, A. P. N. Themmen, and Ch. Sultan Mutant Luteinizing Hormone Receptors in a Compound Heterozygous Patient with Complete Leydig Cell Hypoplasia: Abnormal Processing Causes Signaling Deficiency J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2506 - 2513. [Abstract] [Full Text] [PDF]
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M. Ascoli, F. Fanelli, and D. L. Segaloff The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective Endocr. Rev., April 1, 2002; 23(2): 141 - 174. [Abstract] [Full Text] [PDF]
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G. Smits, C. Govaerts, I. Nubourgh, L. Pardo, G. Vassart, and S. Costagliola Lysine 183 and Glutamic Acid 157 of the TSH Receptor: Two Interacting Residues with a Key Role in Determining Specificity toward TSH and Human CG Mol. Endocrinol., April 1, 2002; 16(4): 722 - 735. [Abstract] [Full Text] [PDF]
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A. Rannikko, P. Pakarinen, P. R. Manna, I. Beau, M. Misrahi, K. Aittomaki, and I. Huhtaniemi Functional characterization of the human FSH receptor with an inactivating Ala189Val mutation Mol. Hum. Reprod., April 1, 2002; 8(4): 311 - 317. [Abstract] [Full Text] [PDF]
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A. Richter-Unruh, H. T. Wessels, U. Menken, M. Bergmann, K. Schmittmann-Ohters, J. Schaper, S. Tappeser, and B. P. Hauffa Male LH-Independent Sexual Precocity in a 3.5-Year-Old Boy Caused by a Somatic Activating Mutation of the LH Receptor in a Leydig Cell Tumor J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1052 - 1056. [Abstract] [Full Text] [PDF]
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E. Doherty, P. Pakarinen, A. Tiitinen, A. Kiilavuori, I. Huhtaniemi, S. Forrest, and K. Aittomaki A Novel Mutation in the FSH Receptor Inhibiting Signal Transduction and Causing Primary Ovarian Failure J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1151 - 1155. [Abstract] [Full Text] [PDF]
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T. Hirakawa, C. Galet, and M. Ascoli MA-10 Cells Transfected with the Human Lutropin/Choriogonadotropin Receptor (hLHR): A Novel Experimental Paradigm to Study the Functional Properties of the hLHR Endocrinology, March 1, 2002; 143(3): 1026 - 1035. [Abstract] [Full Text] [PDF]
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 P. R. Manna, L. Joshi, V. N. Reinhold, M. L. Aubert, N. Suganuma, K. Pettersson, and I. T. Huhtaniemi Synthesis, purification and structural and functional characterization of recombinant form of a common genetic variant of human luteinizing hormone Hum. Mol. Genet., February 1, 2002; 11(3): 301 - 315. [Abstract] [Full Text] [PDF]
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