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The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology¹

Institute of Reproductive Medicine of the University, Domagkstraße 11, D-48129 Münster, Germany

I. Introduction

II. Biochemical Properties of the FSH Receptor: A Historical Prelude

III. Molecular Structure of the FSH Receptor

A. Cloning of the FSH receptor

B. Predicted primary structure of the FSH receptor

C. Molecular mass of the FSH receptor

IV. The FSH Receptor Gene

A. Chromosomal localization

B. Structure and organization of the FSH receptor gene

C. The promoter of the FSH receptor gene

V. Expression of the FSH Receptor and Its Regulation

A. FSH receptor gene expression

B. Expression of the FSH receptor in the testis

C. Expression of the FSH receptor in the ovary

VI. Expression of the FSH Receptor in Cell Lines

A. Cell lines expressing the recombinant FSH receptor

B. Measurement of FSH by means of "recombinant" in vitro bioassays

C. FSH receptor function in cell lines

VII. Structure-Function Relationships and Models of FSH-FSH Receptor Interaction

A. General features

B. Structure-function relationships

C. Models of FSH-FSH receptor interaction

VIII. Signal Transduction and Postreceptor Events

A. Properties of FSH-receptor binding

B. Role of receptor glycosylation and "cryptic" receptors

C. Signal transduction

D. Receptor desensitization

E. Postreceptor events

IX. Inhibitors and Modulators of the FSH Receptor

X. Naturally Occurring Mutations of the FSH Receptor

A. Inactivating mutations

B. Activating mutations

C. Allelic variants

XI. Conclusions

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				G. Meduri, N. Charnaux, M.-A. Driancourt, L. Combettes, P. Granet, B. Vannier, H. Loosfelt, and E. Milgrom Follicle-Stimulating Hormone Receptors in Oocytes? J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2266 - 2276. [Abstract] [Full Text] [PDF]

				S. Chu, S. Rushdi, E.T. Zumpe, P. Mamers, D.L. Healy, T. Jobling, H.G. Burger, and P.J. Fuller FSH-regulated gene expression profiles in ovarian tumours and normal ovaries Mol. Hum. Reprod., May 1, 2002; 8(5): 426 - 433. [Abstract] [Full Text] [PDF]

				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]

				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]

				C. S. Choong, P. J. Fuller, S. Chu, Y. Jeske, F. Bowling, R. Brown, P. Borzi, N. D. Balazs, R. Suppiah, A. M. Cotterill, et al. Sertoli-Leydig Cell Tumor of the Ovary, a Rare Cause of Precocious Puberty in a 12-Month-Old Infant J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 49 - 56. [Abstract] [Full Text] [PDF]

				O. Hovatta, V. Soderstrom-Anttila, T. Foudila, L. Tuomivaara, K. Juntunen, A. Tiitinen, and K. Aittomaki Pregnancies after oocyte donation in women with ovarian failure caused by an inactivating mutation in the follicle stimulating hormone receptor Hum. Reprod., January 1, 2002; 17(1): 124 - 127. [Abstract] [Full Text] [PDF]

				S. Marion, F. Robert, P. Crepieux, N. Martinat, C. Troispoux, F. Guillou, and E. Reiter G Protein-Coupled Receptor Kinases and Beta Arrestins Are Relocalized and Attenuate Cyclic 3',5'-Adenosine Monophosphate Response to Follicle-Stimulating Hormone in Rat Primary Sertoli Cells Biol Reprod, January 1, 2002; 66(1): 70 - 76. [Abstract] [Full Text]

				T. M. Plant and G. R. Marshall The Functional Significance of FSH in Spermatogenesis and the Control of Its Secretion in Male Primates Endocr. Rev., December 1, 2001; 22(6): 764 - 786. [Abstract] [Full Text] [PDF]

				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]

				R. S. Kumar, S. Ijiri, and J. M. Trant Molecular Biology of the Channel Catfish Gonadotropin Receptors: 2. Complementary DNA Cloning, Functional Expression, and Seasonal Gene Expression of the Follicle-Stimulating Hormone Receptor Biol Reprod, September 1, 2001; 65(3): 710 - 717. [Abstract] [Full Text] [PDF]

				W. A. Roscoe, K. J. Barr, A. Amir Mhawi, D. K. Pomerantz, and G. M. Kidder Failure of Spermatogenesis in Mice Lacking Connexin43 Biol Reprod, September 1, 2001; 65(3): 829 - 838. [Abstract] [Full Text] [PDF]

				S. Neumann, G. Krause, S. Chey, and R. Paschke A Free Carboxylate Oxygen in the Side Chain of Position 674 in Transmembrane Domain 7 Is Necessary for TSH Receptor Activation Mol. Endocrinol., August 1, 2001; 15(8): 1294 - 1305. [Abstract] [Full Text] [PDF]

				H. Krishnamurthy, P. Suresh Babu, C. R. Morales, and M. R. Sairam Delay in Sexual Maturity of the Follicle-Stimulating Hormone Receptor Knockout Male Mouse Biol Reprod, August 1, 2001; 65(2): 522 - 531. [Abstract] [Full Text] [PDF]

				F. Clement, D. Monniaux, J. Stark, K. Hardy, J. C. Thalabard, S. Franks, and D. Claude Mathematical model of FSH-induced cAMP production in ovarian follicles Am J Physiol Endocrinol Metab, July 1, 2001; 281(1): E35 - E53. [Abstract] [Full Text] [PDF]

				K. M. Fox, J. A. Dias, and P. Van Roey Three-Dimensional Structure of Human Follicle-Stimulating Hormone Mol. Endocrinol., March 1, 2001; 15(3): 378 - 389. [Abstract] [Full Text]

				R. Sampath Kumar, S. Ijiri, and J. M. Trant Molecular Biology of Channel Catfish Gonadotropin Receptors: 1. Cloning of a Functional Luteinizing Hormone Receptor and Preovulatory Induction of Gene Expression Biol Reprod, March 1, 2001; 64(3): 1010 - 1018. [Abstract] [Full Text]

				W. Xing and M. Ram Sairam Characterization of Regulatory Elements of Ovine Follicle-Stimulating Hormone (FSH) Receptor Gene: The Role of E-Box in the Regulation of Ovine FSH Receptor Expression Biol Reprod, February 1, 2001; 64(2): 579 - 589. [Abstract] [Full Text]

				P. S. Babu, N. Danilovich, and M. R. Sairam Hormone-Induced Receptor Gene Splicing: Enhanced Expression of the Growth Factor Type I Follicle-Stimulating Hormone Receptor Motif in the Developing Mouse Ovary as a New Paradigm in Growth Regulation Endocrinology, January 1, 2001; 142(1): 381 - 389. [Abstract] [Full Text] [PDF]

				S. K. Roy and L. Albee Requirement for Follicle-Stimulating Hormone Action in the Formation of Primordial Follicles during Perinatal Ovarian Development in the Hamster Endocrinology, December 1, 2000; 141(12): 4449 - 4456. [Abstract] [Full Text] [PDF]

				L. L. Heckert, M. Sawadogo, M. A. F. Daggett, and J. k. Chen The USF Proteins Regulate Transcription of the Follicle-Stimulating Hormone Receptor but Are Insufficient for Cell- Specific Expression Mol. Endocrinol., November 1, 2000; 14(11): 1836 - 1848. [Abstract] [Full Text]

				A. P. N. Themmen and I. T. Huhtaniemi Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function Endocr. Rev., October 1, 2000; 21(5): 551 - 583. [Abstract] [Full Text]

				U. A. Vitt, E. A. McGee, M. Hayashi, and A. J. W. Hsueh In Vivo Treatment with GDF-9 Stimulates Primordial and Primary Follicle Progression and Theca Cell Marker CYP17 in Ovaries of Immature Rats Endocrinology, October 1, 2000; 141(10): 3814 - 3820. [Abstract] [Full Text] [PDF]

				M. P. Mayorga, J. Gromoll, H. M. Behre, C. Gassner, E. Nieschlag, and M. Simoni Ovarian Response to Follicle-Stimulating Hormone (FSH) Stimulation Depends on the FSH Receptor Genotype J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3365 - 3369. [Abstract] [Full Text]