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Molecular Endocrinology Vol. 4, No. 4 525-530
doi:10.1210/mend-4-4-525
Copyright © 1990 by the Endocrine Society.
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The Testicular Receptor for Follicle Stimulating Hormone: Structure and Functional Expression of Cloned cDNA

Rolf Sprengel, Thomas Braun*, Karoly Nikolics, Deborah L. Segaloff and Peter H. Seeburg

University Heidelberg, Zentrum für Molekulare Biologie, Laboratory of Molecular Neuroendocrinology D-6900 Heidelberg 1, Federal Republic of Germany
Genentech Inc., Department of Developmental Biology South San Francisco, California 90480
The Population Council New York, New York 10021

Address requests for reprints to: Peter H. Seeburg, Zentrum für Molekulare Biologie, Universität Heidelburg Im Neuenheimer Feld 282, D-6900 Heidelberg, Federal Republic of Germany.

Abstract

Cloned cDNA encoding the rat Sertoli cell receptor for FSH was isolated from a cognate library and functionally expressed in cultured mammalian cells. The FSH receptor (FSH-R), as predicted from the cDNA, is a single 75K polypeptide with a 348 residue extracellular domain which contains three N-linked glycosylation sites. This domain is connected to a structure containing seven putative transmembrane segments which displays sequence similarity to G protein-coupled receptors. Thus, the FSH-R is identical in its structural design to the LH/CG receptor (LH/CG-R). Furthermore, both receptors display 50% sequence similarity in their large extracellular domains and 80% identity across the seven transmembrane segments. Expression of the cloned cDNA in mammalian cells conferred FSH-dependent cAMP accumulation. The selectivity for FSH is attested by the fact that the related human glycoprotein hormones human CG and human TSH do not stimulate adenylyl cyclase in FSH-R expressing cells even when these hormones are present at high concentrations.

FOOTNOTES

This work was funded by the Deutsche Forschungsgemeinschaft and the German Ministry for Research and Technology (to P.H.S.) and by NIH Grant HD-22196 (to D.L.S.).

* Recipient of a doctoral training grant by Boehringer Ingelheim.

Received for publication January 19, 1990. Accepted for publication January 19, 1990.




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Signaling and Phosphorylation-impaired Mutants of the Rat Follitropin Receptor Reveal an Activation- and Phosphorylation-independent but Arrestin-dependent Pathway for Internalization
J. Biol. Chem., September 18, 1998; 273(38): 24346 - 24354.
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A. O. L. Wong, M. Y. Leung, W. L. C. Shea, L. Y. Tse, J. P. Chang, and B. K. C. Chow
Hypophysiotropic Action of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Goldfish: Immunohistochemical Demonstration of PACAP in the Pituitary, PACAP Stimulation of Growth Hormone Release from Pituitary Cells, and Molecular Cloning of Pituitary Type I PACAP Receptor
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D.A. Douglas, A. Houde, J.H. Song, R. Farookhi, P.W. Concannon and, and B.D. Murphy
Luteotropic Hormone Receptors in the Ovary of the Mink (Mustela vison) during Delayed Implantation and Early-Postimplantation Gestation
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A. Mukherjee, J. Urban, P. Sassone-Corsi, and K. E. Mayo
Gonadotropins Regulate Inducible Cyclic Adenosine 3',5'-Monophosphate Early Repressor in the Rat Ovary: Implications for Inhibin {alpha} Subunit Gene Expression
Mol. Endocrinol., June 1, 1998; 12(6): 785 - 800.
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Rilianawati, T. Paukku, J. Kero, F.-P. Zhang, N. Rahman, K. Kananen, and I. Huhtaniemi
Direct Luteinizing Hormone Action Triggers Adrenocortical Tumorigenesis in Castrated Mice Transgenic for The Murine Inhibin {alpha}-Subunit Promoter/Simian Virus 40 T-Antigen Fusion Gene
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S. S. Stavrou, Y.-S. Zhu, L.-Q. Cai, M. D. Katz, C. Herrera, M. DeFillo-Ricart, and J. Imperato-McGinley
A Novel Mutation of the Human Luteinizing Hormone Receptor in 46XY and 46XX Sisters
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K. Nakamura, R. W. Hipkin, and M. Ascoli
The Agonist-Induced Phosphorylation of the Rat Follitropin Receptor Maps to the First and Third Intracellular Loops
Mol. Endocrinol., April 1, 1998; 12(4): 580 - 591.
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 EndocrinologyHome page
T. G. Rozell, D. P. Davis, Y. Chai, and D. L. Segaloff
Association of Gonadotropin Receptor Precursors with the Protein Folding Chaperone Calnexin
Endocrinology, April 1, 1998; 139(4): 1588 - 1593.
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C. Racine, R. Rey, M. G. Forest, F. Louis, A. Ferre, I. Huhtaniemi, N. Josso, and N. di Clemente
Receptors for anti-Mullerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation
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M. Simoni, J. Gromoll, and E. Nieschlag
The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology
Endocr. Rev., December 1, 1997; 18(6): 739 - 773.
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K. Oktay, D. Briggs, and R. G. Gosden
Ontogeny of Follicle-Stimulating Hormone Receptor Gene Expression in Isolated Human Ovarian Follicles
J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3748 - 3751.
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Y. Osuga, M. Hayashi, M. Kudo, M. Conti, B. Kobilka, and A. J. W. Hsueh
Co-expression of Defective Luteinizing Hormone Receptor Fragments Partially Reconstitutes Ligand-induced Signal Generation
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A. Amsterdam and N. Selvaraj
Control of Differentiation, Transformation, and Apoptosis in Granulosa Cells by Oncogenes, Oncoviruses, and Tumor Suppressor Genes
Endocr. Rev., August 1, 1997; 18(4): 435 - 461.
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F.-P. Zhang, A. S. Rannikko, P. R. Manna, H. M. Fraser, and I. T. Huhtaniemi
Cloning and Functional Expression of the Luteinizing Hormone Receptor Complementary Deoxyribonucleic Acid from the Marmoset Monkey Testis: Absence of Sequences Encoding Exon 10 in Other Species
Endocrinology, June 1, 1997; 138(6): 2481 - 2490.
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 Mol. Endocrinol.Home page
D. P. Davis, T. G. Rozell, X. Liu, and D. L. Segaloff
The Six N-linked Carbohydrates of the Lutropin/Choriogonadotropin Receptor Are Not Absolutely Required for Correct Folding, Cell Surface Expression, Hormone Binding, or Signal Transduction
Mol. Endocrinol., May 1, 1997; 11(5): 550 - 562.
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F. Hauser, H.-P. Nothacker, and C. J.P. Grimmelikhuijzen
Molecular Cloning, Genomic Organization, and Developmental Regulation of a Novel Receptor from Drosophila melanogaster Structurally Related to Members of the Thyroid-stimulating Hormone, Follicle-stimulating Hormone, Luteinizing Hormone/Choriogonadotropin Receptor Family from Mammals
J. Biol. Chem., January 10, 1997; 272(2): 1002 - 1010.
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T. L. Goetz, T. L. Lloyd, and M. D. Griswold
Role of E Box and Initiator Region in the Expression of the Rat Follicle-stimulating Hormone Receptor
J. Biol. Chem., December 27, 1996; 271(52): 33317 - 33324.
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R. Zhang, E. Buczko, and M. L. Dufau
Requirement of Cysteine Residues in Exons 1-6 of the Extracellular Domain of the Luteinizing Hormone Receptor for Gonadotropin Binding
J. Biol. Chem., March 8, 1996; 271(10): 5755 - 5760.
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A. Abell, X. Liu, and D. L. Segaloff
Deletions of Portions of the Extracellular Loops of the Lutropin/Choriogonadotropin Receptor Decrease the Binding Affinity for Ovine Luteinizing Hormone, but Not Human Choriogonadotropin, by Preventing the Formation of Mature Cell Surface Receptor
J. Biol. Chem., February 23, 1996; 271(8): 4518 - 4527.
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J. Couet, S. Sar, A. Jolivet, M.-T. V. Hai, E. Milgrom, and M. Misrahi
Shedding of Human Thyrotropin Receptor Ectodomain
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G. B. Bolger, I. McPhee, and M. D. Houslay
Alternative Splicing of cAMP-specific Phosphodiesterase mRNA Transcripts
J. Biol. Chem., January 12, 1996; 271(2): 1065 - 1071.
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R. W. Hipkin, X. Liu, and M. Ascoli
Truncation of the C-terminal Tail of the Follitropin Receptor Does Not Impair the Agonist- or Phorbol Ester-induced Receptor Phosphorylation and Uncoupling
J. Biol. Chem., November 3, 1995; 270(44): 26683 - 26689.
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L. Cosowsky, S. N. V. Rao, G. J. Macdonald, H. Papkoff, R. K. Campbell, and W. R. Moyle
The Groove between the alpha- and beta-Subunits of Hormones with Lutropin (LH) Activity Appears to Contact the LH Receptor, and Its Conformation Is Changed during Hormone Binding
J. Biol. Chem., August 25, 1995; 270(34): 20011 - 20019.
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I. Ji and T. H. Ji
Differential Roles of Exoloop 1 of the Human Follicle-stimulating Hormone Receptor in Hormone Binding and Receptor Activation
J. Biol. Chem., July 7, 1995; 270(27): 15970 - 15973.
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 DevelopmentHome page
W. Baarends, M. van Helmond, M Post, P. van der Schoot, J. Hoogerbrugge, J. de Winter, J. Uilenbroek, B Karels, L. Wilming, J. Meijers, et al.
A novel member of the transmembrane serine/threonine kinase receptor family is specifically expressed in the gonads and in mesenchymal cells adjacent to the mullerian duct
Development, January 1, 1994; 120(1): 189 - 197.
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 ScienceHome page
H. Wadsworth, G. Chazenbalk, Y Nagayama, D Russo, and B Rapoport
An insertion in the human thyrotropin receptor critical for high affinity hormone binding
Science, September 21, 1990; 249(4975): 1423 - 1425.
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P. S. Babu, H. Krishnamurthy, P. J. Chedrese, and M. R. Sairam
Activation of Extracellular-regulated Kinase Pathways in Ovarian Granulosa Cells by the Novel Growth Factor Type 1 Follicle-stimulating Hormone Receptor. ROLE IN HORMONE SIGNALING AND CELL PROLIFERATION
J. Biol. Chem., September 1, 2000; 275(36): 27615 - 27626.
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Y. S. Song, I. Ji, J. Beauchamp, N. W. Isaacs, and T. H. Ji
Hormone Interactions to Leu-rich Repeats in the Gonadotropin Receptors. I. ANALYSIS OF LEU-RICH REPEATS OF HUMAN LUTEINIZING HORMONE/CHORIONIC GONADOTROPIN RECEPTOR AND FOLLICLE-STIMULATING HORMONE RECEPTOR
J. Biol. Chem., January 26, 2001; 276(5): 3426 - 3435.
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H. Kishi and M. Ascoli
Multiple Distant Amino Acid Residues Present in the Serpentine Region of the Follitropin Receptor Modulate the Rate of Agonist-induced Internalization
J. Biol. Chem., September 29, 2000; 275(40): 31030 - 31037.
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R. Seger, T. Hanoch, R. Rosenberg, A. Dantes, W. E. Merz, J. F. Strauss III, and A. Amsterdam
The ERK Signaling Cascade Inhibits Gonadotropin-stimulated Steroidogenesis
J. Biol. Chem., April 20, 2001; 276(17): 13957 - 13964.
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F. Otsuka, S. Yamamoto, G. F. Erickson, and S. Shimasaki
Bone Morphogenetic Protein-15 Inhibits Follicle-stimulating Hormone (FSH) Action by Suppressing FSH Receptor Expression
J. Biol. Chem., March 30, 2001; 276(14): 11387 - 11392.
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F. Otsuka, R. K. Moore, and S. Shimasaki
Biological Function and Cellular Mechanism of Bone Morphogenetic Protein-6 in the Ovary
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