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Department of Physiology (F.-P.Z., M.P., I.H.) Institute of
Biomedicine University of Turku FIN-20520, Turku, Finland
Department of Cell and Molecular Biology (J.W.) Karolinska
Institute S-17177 Stockholm, Sweden
To study further the role of gonadotropins in reproductive functions, we generated mice with LH receptor (LHR) knockout (LuRKO) by inactivating, through homologous recombination, exon 11 on the LHR gene. LuRKO males and females were born phenotypically normal, with testes, ovaries, and genital structures indistinguishable from their wild-type (WT) littermates. Postnatally, testicular growth and descent, and external genital and accessory sex organ maturation, were blocked in LuRKO males, and their spermatogenesis was arrested at the round spermatid stage. The number and size of Leydig cells were dramatically reduced. LuRKO females also displayed underdeveloped external genitalia and uteri postnatally, and their age of vaginal opening was delayed by 57 days. The (-/-) ovaries were smaller, and histological analysis revealed follicles up to the early antral stage, but no preovulatory follicles or corpora lutea. Reduced gonadal sex hormone production was found in each sex, as was also reflected by the suppressed accessory sex organ weights and elevated gonadotropin levels. Completion of meiosis of testicular germ cells in the LuRKO males differs from other hypogonadotropic/cryptorchid mouse models, suggesting a role for FSH in this process. In females, FSH appears to stimulate developing follicles from the preantral to early antral stage, and LH is the stimulus beyond this stage. Hence, in each sex, the intrauterine sex differentiation is independent of LH action, but it has a crucial role postnatally for attaining sexual maturity. The LuRKO mouse is a close phenocopy of recently characterized human patients with inactivating LHR mutations, although the lack of pseudohermaphroditism in LuRKO males suggests that the intrauterine sex differentiation in this species is not dependent on LH action.
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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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P. J. Baker, P. Pakarinen, I. T. Huhtaniemi, M. H. Abel, H. M. Charlton, T. R. Kumar, and P. J. O'Shaughnessy Failure of Normal Leydig Cell Development in Follicle-Stimulating Hormone (FSH) Receptor-Deficient Mice, But Not FSH{beta}-Deficient Mice: Role for Constitutive FSH Receptor Activity Endocrinology, January 1, 2003; 144(1): 138 - 145. [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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M. Haywood, N. Tymchenko, J. Spaliviero, A. Koch, M. Jimenez, J. Gromoll, M. Simoni, V. Nordhoff, D. J. Handelsman, and C. M. Allan An Activated Human Follicle-Stimulating Hormone (FSH) Receptor Stimulates FSH-Like Activity in Gonadotropin-Deficient Transgenic Mice Mol. Endocrinol., November 1, 2002; 16(11): 2582 - 2591. [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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G. E. Owens, R. A. Keri, and J. H. Nilson Ovulatory Surges of Human CG Prevent Hormone-Induced Granulosa Cell Tumor Formation Leading to the Identification of Tumor-Associated Changes in the Transcriptome Mol. Endocrinol., June 1, 2002; 16(6): 1230 - 1242. [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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C. Romero, A. Paredes, G. A. Dissen, and S. R. Ojeda Nerve Growth Factor Induces the Expression of Functional FSH Receptors in Newly Formed Follicles of the Rat Ovary Endocrinology, April 1, 2002; 143(4): 1485 - 1494. [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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P. J. O'Shaughnessy, H. Johnston, L. Willerton, and P. J. Baker Failure of normal adult Leydig cell development in androgen-receptor-deficient mice J. Cell Sci., January 9, 2002; 115(17): 3491 - 3496. [Abstract] [Full Text] [PDF] |
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I. A. Hughes Minireview: Sex Differentiation Endocrinology, August 1, 2001; 142(8): 3281 - 3287. [Abstract] [Full Text] [PDF] |
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F. El-Gehani, M. Tena-Sempere, H. Ruskoaho, and I. Huhtaniemi Natriuretic Peptides Stimulate Steroidogenesis in the Fetal Rat Testis Biol Reprod, August 1, 2001; 65(2): 595 - 600. [Abstract] [Full Text] [PDF] |
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S. B. Seminara and W. F. Crowley Jr. Perspective: The Importance of Genetic Defects in Humans in Elucidating the Complexities of the Hypothalamic-Pituitary-Gonadal Axis Endocrinology, June 1, 2001; 142(6): 2173 - 2177. [Full Text] [PDF] |
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J. S. Richards Perspective: The Ovarian Follicle--A Perspective in 2001 Endocrinology, June 1, 2001; 142(6): 2184 - 2193. [Full Text] [PDF] |
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