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Department of Human Anatomy and Genetics, University of Oxford (M.H.A., A.N.W., V.W., H.M.C.), Oxford, United Kingdom OX1 3QX; Department of Physiology, Institute of Biomedicine, University of Turku (I.H.), 20502 Turku, Finland; and School of Animal and Microbial Sciences, University of Reading (P.G.K.), Whiteknights, Reading, United Kingdom RG6 6AJ
Address all correspondence and requests for reprints to: Dr. Margaret H. Abel, Department of Human Anatomy and Genetics, University of Oxford, Oxford, United Kingdom OX1 3QX. E-mail: margaret.abel{at}anat.ox.ac.uk
To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vagina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the serum and gonads. Compared with those in control animals, serum concentrations of FSH and LH were significantly elevated in mutant females. The pituitary content of FSH, but not LH, was also significantly elevated. Estrogen administration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mice were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in normal littermates. Serum levels of FSH and LH were elevated in the null mutant male mice, whereas no differences were found in the pituitary content of these hormones. In conclusion, ovarian follicular development cannot progress beyond the preantral stage without FSH. In the absence of mature follicles ovarian estrogen remains low, and consequently accessory sex tissue growth and negative feedback regulation of gonadotropin secretion are severely compromised. In the male, however, inability to respond to FSH does not impair fertility, although testicular weight is reduced, and feedback regulation of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.
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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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B. J. Arey, D. C. Deecher, E. S. Shen, P. E. Stevis, E. H. Meade Jr, J. Wrobel, D. E. Frail, and F. J. Lopez Identification and Characterization of a Selective, Nonpeptide Follicle-Stimulating Hormone Receptor Antagonist Endocrinology, October 1, 2002; 143(10): 3822 - 3829. [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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W. Xing and M. R. Sairam Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element Biol Reprod, July 1, 2002; 67(1): 204 - 211. [Abstract] [Full Text] [PDF]
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W. Yan, A. Rajkovic, M. M. Viveiros, K. H. Burns, J. J. Eppig, and M. M. Matzuk Identification of Gasz, an Evolutionarily Conserved Gene Expressed Exclusively in Germ Cells and Encoding a Protein with Four Ankyrin Repeats, a Sterile-{alpha} Motif, and a Basic Leucine Zipper Mol. Endocrinol., June 1, 2002; 16(6): 1168 - 1184. [Abstract] [Full Text] [PDF]
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W. Xing and M. R. Sairam Role of CACC-Box in the Regulation of Ovine Follicle-Stimulating Hormone Receptor Expression Biol Reprod, October 1, 2001; 65(4): 1142 - 1149. [Abstract] [Full Text] [PDF]
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N. Danilovich, I. Roy, and M. R. Sairam Ovarian Pathology and High Incidence of Sex Cord Tumors in Follitropin Receptor Knockout (FORKO) Mice Endocrinology, August 1, 2001; 142(8): 3673 - 3684. [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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I. Huhtaniemi and A. Bartke Perspective: Male Reproduction Endocrinology, June 1, 2001; 142(6): 2178 - 2183. [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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C. M. Allan, M. Haywood, S. Swaraj, J. Spaliviero, A. Koch, M. Jimenez, M. Poutanen, J. Levallet, I. Huhtaniemi, P. Illingworth, et al. A Novel Transgenic Model to Characterize the Specific Effects of Follicle-Stimulating Hormone on Gonadal Physiology in the Absence of Luteinizing Hormone Actions Endocrinology, June 1, 2001; 142(6): 2213 - 2220. [Abstract] [Full Text] [PDF]
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K. F. Roby Alterations in Follicle Development, Steroidogenesis, and Gonadotropin Receptor Binding in a Model of Ovulatory Blockade Endocrinology, June 1, 2001; 142(6): 2328 - 2335. [Abstract] [Full Text] [PDF]
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J. Levallet, P. Koskimies, N. Rahman, and I. Huhtaniemi The Promoter of Murine Follicle-Stimulating Hormone Receptor: Functional Characterization and Regulation by Transcription Factor Steroidogenic Factor 1 Mol. Endocrinol., January 1, 2001; 15(1): 80 - 92. [Abstract] [Full Text]
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F.-P. Zhang, M. Poutanen, J. Wilbertz, and I. Huhtaniemi Normal Prenatal but Arrested Postnatal Sexual Development of Luteinizing Hormone Receptor Knockout (LuRKO) Mice Mol. Endocrinol., January 1, 2001; 15(1): 172 - 183. [Abstract] [Full Text]
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Z. M. Lei, S. Mishra, W. Zou, B. Xu, M. Foltz, X. Li, and Ch. V. Rao Targeted Disruption of Luteinizing Hormone/Human Chorionic Gonadotropin Receptor Gene Mol. Endocrinol., January 1, 2001; 15(1): 184 - 200. [Abstract] [Full Text]
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 L Zhao, M Bakke, Y Krimkevich, L. Cushman, A. Parlow, S. Camper, and K. Parker Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function Development, January 1, 2001; 128(2): 147 - 154. [Abstract] [PDF]
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