Novel insights into the molecular mechanisms of human thyrotropin action: Structural, physiological, and therapeutic implications for the glycoprotein hormone family

Endocrine Reviews

Volumn 18, Issue 4, 1997, Pages 476-501

  Grossmann, Mathis ^a   Weintraub, Bruce D ^a   Szkudlinski, Mariusz W ^a,b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b INSTITUTE OF HUMAN VIROLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN; THYROTROPIN;

EVOLUTION; HORMONE RECEPTOR INTERACTION; HUMAN; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; THYROTROPIN RELEASE;

EID: 0030852648     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/edrv.18.4.0305     Document Type: Review

References (238)

1. Magner JA 1990 Thyroid-stimulating hormone: biosynthesis, cell biology and bioactivity. Endocr Rev 11:354-385
2. Magner JA 1994 Biosynthesis, cell biology, and bioactivity of thyroid-stimulating hormone: update 1994. In: Braverman LE, Refetoff S (eds) Endocrine Reviews Monographs. The Endocrine Society, Rockville, MD, vol 3:55-60
3. Pierce JG, Parsons TF 1981 Glycoprotein hormones: structure and function. Annu Rev Biochem 50:465-495
4. Green ED, Baenziger JU 1988 Asparagine-linked oligosaccharides on lutropin, follitropin and thyrotropin. I. Structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine and human glycoprotein hormones. J Biol Chem 263:25-35
5. Baenziger JU 1994 Glycosylation and glycoprotein hormone function. In: Lustbander JW, Puett D, Ruddon RW (eds) Glycoprotein Hormones: Structure, Function and Clinical Implications. Springer- Verlag, New York, pp 167-174
6. Fiddes JC, Goodman HM 1979 Isolation, cloning and sequence analysis of the cDNA for the α-subunit of human chorionic gonadotropin. Nature 281:351-356
7. Hayashizaki Y, Miyai K, Kato K, Matsubara K 1985 Molecular cloning of the human thyrotropin β-subunit gene. FEBS Lett 188: 394-400
8. Wondisford FE, Radovick S, Moates JM, Usala SJ, Weintraub BD 1988 Isolation and characterization of the human thyrotropin β-subunit gene. Differences in gene stucture and promoter function from murine species. J Biol Chem 263:12538-12542
9. Wondisford FE, Usala SJ, DeChemey SG, Castren M, Radovick S, Gyves PW, Trempe JP, Kerfoot BP, Nikodem VM, Carter BJ, Weintraub BD 1988 Cloning of the human thyrotropin β-subunit gene and transient expression of biologically active human thyrotropin after gene transfection. Mol Endocrinol 2:32-39
10. Parmentier M, Libert F, Maenhaut C, Lefort A, Gerard C, Perret J, Van Sande J, Dumont JE, Vassart G 1989 Molecular cloning of the thyrotropin receptor. Science 246:1620-1622
11. Nagayama Y, Kaufman KD, Seto P, Rapoport B 1989 Molecular cloning, sequence and functional expression of he thyrotropin receptor. Biochem Biophys Res Commun 165:1184-1190
12. Misrahi M, Loosfelt H, Atger M, Sar S, Guiochon-Mantel A, Milgrom E 1990 Cloning, sequencing and expression of human TSH receptor. Biochem Biophys Res Commun 166:394-403
13. Libert F, Lefort A, Gerard C, Parmentier M Perret J, Ludgate M, Dumont JE, Vassart G 1989 Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for the binding of autoantibodies. Biochem Biophys Res Commun 165:1250- 1255
14. Cole ES, Lee K, Lauziere K, Kelton C, Chappel S, Weintraub BD, Ferrara D, Peterson P, Bernasconi R, Edmunds T, Richards S, Dickrell L, Kleemann JM, McPherson JM, Pratt BM 1993 Recombinant human thyroid stimulating hormone: development of a biotechnology product for detection of metastatic lesions of thyroid carcinoma. Bio / technology 11:1014-1024
15. Meier CA, Braverman LE, Ebner SA, Veronikis I, Daniels GH, Ross DS, Deraska DJ, Davies TF, Valentine M, DeGroot LJ, Curran P, McEllin K, Reynolds J, Robbins J, Weintraub BD 1994 Diagnostic use of recombinant human thyrotropin in patients with thyroid carcinoma (phase I/II study). J Clin Endocrinol Metab 78:188-196
16. Ladenson PW, Braverman LE, Mazzaferri EL, Robbins J, Cooper DS, Garber JR, Wondisford FE, Davies TF, DeGroot LJ, Daniels GH, Ross DS, Hay ID, Levis S, Brucker-Davis F, Reynolds JC, Becker DV, Cavalieri RR, Maxon HR, McEllin K, Moscicki R, Weintraub BD, Comparison of recombinant human thyrotropin administration to thyroid hormone withdrawal for radioactive iodine scanning in patients with thyroid carcinoma. N Engl J Med, in press
17. Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ, Isaacs NW1994 Crystal structure of human chorionic gonadotropin. Nature 369:455-461
18. Wu H, Lustbader JW, Liu Y, Canfield RE, Hendrickson WA 1994 Structure of human chorionic gonadotropin at 2.6 Å resolution from MAD analysis of the selenomethionyl protein. Structure 2:545-558
19. Kobe B, Deisenhofer J 1995 A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature 374:183- 186
20. McFarland KC, Sprengel R, Phillips HS, Köhler M, Rosemblit N, Nikolics K, Segaloff DL, Seeburg PH 1989 Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science 245:494-499
21. Segaloff DL, Ascoli M 1993 The lutropin / choriogonadotropin receptor. . . 4 years later. Endocr Rev 14:324-347
22. Shupnik MA, Ridgway EC, Chin WW 1989 Molecular biology of human thyrotropin. Endocr Rev 10:459-475
23. Shupnik MA, Ridgway EC, Chin WW 1994 Thyrotropin molecular biology: update 1994. In: Braverman LE, Refetoff S (eds) Endocrine Reviews Monographs. The Endocrine Society, Rockville, MD, vol 3:18:22
24. Jameson JL, Hollenberg AN 1993 Regulation of chorionic gonadotropin gene expression. Endocr Rev 14:203-221
25. Nilson JH 1994 Molecular mechanisms underlying placenta- and pituitary- specific expression of the glycoprotein hormone α-subunit gene. In: Lustbader JW, Puett D, Ruddon RW (eds) Glycoprotein Hormones: Structure, Function and Clinical Implications. Springer-Verlag, New York, pp 39-49
26. Weintraub BD, Kim MD, Bodenner DL, Thotakura NR, Szkudlinski MW, Joshi L, Murata Y 1994 Regulation and expression of thyroid-stimulating hormone. In: Lustbader JW, Puett JD, Ruddon RW (eds) Glycoprotein Hormones: Structure, Function and Clinical Implications. Springer-Verlag, New York, pp 75-78
27. Wondisford FE, Magner JA, Weintraub BD 1996 Thyrotropin. In: Braverman LE, Utiger RD (eds) Werner and Ingbars' The Thyroid. Lippincott-Raven, Philadelphia, pp 190-207
28. Vassart G, Dumont JE 1992 The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev 13:596- 611
29. Vassart G, Parma J, Van Sande J, Dumont JE 1994 The thyrotropin receptor and the regulation of thyrocyte function and growth. Update 1994. In: Braverman LE, Refetoff S (eds) Endocrine Reviews Monographs. The Endocrine Society, Rockville, MD, vol 3:77-80
30. Kohn LD, Shimura M, Shimura Y, Hikada A, Giuliani C, Napolitano G, Ohmori M, Laglia G, Saji M 1995 The thyrotropin receptor. Vitam Horm 50:287-384
31. Nagayama Y, Rapoport B 1992 The thyrotropin receptor 25 years after its discovery: new insights after its molecular cloning. Mol Endocrinol 6:145-156
32. Dumont JE, Lamy F, Roger P, Maenhaut C 1992 Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors. Physiol Rev 72:667-697
33. Kawakami A, Eguchi K, Matsouka N, Tsuboi M, Kawabe Y, Ishikawa N, Ito K, Nagataki S 1996 Thyroid-stimulating hormone inhibits Fas antigen-mediated apoptosis of human thyrocytes in vitra. Endocrinology 137:3163-3169
34. Tilly JL, Tilly KI, Kenton ML, Johnson AL 1995 Expression of members of the Bcl-2 gene family in the immature rat ovary: equine gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased Bax and constitutive Bcl-2 and Bcl-xlong messenger ribonucleic acid levels. Endocrinology 136:232-241
35. Tilly KI, Banerjee PP, Banerjee PP, Tilly JL 1995 Expression of the p53 and Wilms' tumor suppressor genes in the rat ovary: gonadotropin repression in vivo and immunohistochemical localization of nuclear p53 protein to apoptotic granulosa cells of atretic follicles. Endocrinology 136:1394-1402
36. Kendall SK, Samuelson LC, Saunders TL, Wood RI, Camper SA 1995 Targeted disruption of the pituitary glycoprotein hormone α-subunit produces hypogonadal and hypothyroid mice. Genes Dev 9:2007-2019
37. Licht P, Papkoff H, Farmer SW, Muller CH, Tsui HW, Crews D 1976 Evolution of gonadotropin structure and function. Recent Prog Horm Res 33:169-248
38. Fiddes JC, Goodman HM 1980 The cDNA for the β-subunit of human chorionic gonadotropin suggests evolution of a gene by readthrough into the 3′-untranslated region. Nature 286:684- 687
39. Fiddes JC, Goodman HM 1981 The gene encoding the common alpha subunit of the four human glycoprotein hormones. J Mol Appl Gen 1:3-18
40. Takata K, Watanabe S, Hirono M, Tamaki M, Teraoka H, Hayashizaki Y 1989 The role of the carboxyl-terminal 6 amino acid extension of human TSH β subunit. Biochem Biophys Res Commun 165:1035-1042
41. Bahl OP, Thotakura NR, Chen WY 1993 Biological and molecular approaches to modify oligosaccharides: analysis of glycosylation function in human choriogonadotropin. In: Roberts DD, Mechan RP (eds) Cell Surface and Extracellular Glycoconjugates. Academic Press, San Diego, pp 245-271
42. Bielinska M, Boime I 1995 The glycoprotein hormone family: structure and function of the carbohydrate chains. In: Montreuil J, Vliegenhart JFG, Schachter H (eds) Glycoproteins. Elsevier Science BV, Amsterdam, The Netherlands, pp 167-174
43. Baenziger JU 1996 Editorial: Glycosylation: to what end for the glycoprotein hormones? Endocrinology 137:1520-1522
44. Manzella SM, Hooper LV, Baenziger JU 1996 Oligosaccharides containing 1,4-linked N-acetylgalactosamine, a paradigm for protein-specific glycosylation. J Biol Chem 271:12117-12120
45. Sun PD, Davis DR 1995 The cystine-knot growth factor superfamily. Annu Rev Biophys Biomol Struct 24:269-291
46. Szkudlinski MW, Grossmann M, Weintraub BD 1996 Structure- function studies of human TSH: new advances in the design of glycoprotein hormone analogs. Trends Endocrinol Metab 7:277- 286
47. Blithe DL, Richards RG, Skarulis MC 1991 Free alpha molecules from pregnancy stimulate secretion of prolactin from human decidual cells: a novel function for free alpha in pregnancy. Endocrinology 129:2257-2259
48. Bourinbaiar AS, Lee-Huang S 1995 Anti-HIV effect of beta subunit of human chorionic gonadotropin (βhCG) in vitro. Immunol Lett 44:13-18
49. Lunardi-Iskandar Y, Bryant JL, Zeman RA, Lam VH, Samaniego F, Besnier JM, Hermans P, Thierry AR, Gill P, Gallo RC 1995 Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. Nature 375:64-68
50. Szkudlinski MW, Teh NG, Grossmann M, Tropea JE, Weintraub BD 1996 Engineering human glycoprotein hormone superactive analogues. Nat Biotechnol 14:1257-1263
51. Fairlie WD, Stanton PG, Hearn MTW 1996 The disulphide bond structure of thyroid-stimulating hormone β-subunit. Biochem J 314:449-455
52. Gordon WL, Ward DN 1985 Structural aspects of luteinizing hormone actions. In: Ascoli M (ed) Luteinizing Hormone Action and Receptors. CRC Press, Boca Raton, FL, pp 173-197
53. Sairam MR 1989 Role of carbohydrates in glycoprotein hormone signal transduction. FASEB J 3:1915-1926
54. Campbell RK, Matzuk MM, Dean-Emig DM, Cogliani E, Myers- Shamy RV, Krichevsky A, Boime I, Barnett R, Moyle WR 1990 Use of β-subunit chimeras to study the structures of glycoprotein hormones and to develop a model of the β-subunit. In: Chin WW, Boime I (eds) Glycoprotein Hormones. Serono Symposia USA, Norwell MA, pp 37-44
55. Keutmann HT 1992 Receptor-binding regions in human glycoprotein hormones. Mol Cell Endocrinol 86:C1-C6
56. Stockell Hartee A, Renwick AGC 1992 Molecular structures of glycoprotein hormones and functions of their carbohydrate components. Biochem J 287:665-679
57. Combarnous Y 1992 Molecular basis of the specificity of binding of glycoprotein hormones to their receptors. Endocr Rev 13:670- 691
58. Dias JA 1992 Progress and approaches in mapping the surfaces of human follicle-stimulating hormone. Comparison with the other human pituitary glycoprotein hormones. Trends Endocrinol Metab 3:24-29
59. Galway AB, LaPolt P, Boime I, Hsueh AJW1992 Recombinant FSH and regulation of ovulation. In: Hunziker-Dunn M, Schwartz NB (eds) Follicle Stimulating Hormone. Regulation of Secretion and Molecular Mechanism of Action. Springer Verlag, New York, pp 206-214
60. Ji TH, Murdoch WJ, Ji I 1995 Activation of membrane receptors. Endocrine 3:187-194
61. Reichert Jr LE 1994 The functional relationship between FSH and its receptors as studied by synthetic peptide strategies. Mol Cell Endocrinol 100:21-27
62. Lash RW, Desai RK, Zimmermann CA, Flack MR, Yoshida T, Wondisford FE, Weintraub BD 1992 Mutations of the human thyrotropin-β subunit glycosylation site reduce thyrotropin synthesis independent of changes in glycosylation status. J Endocrinol Invest 15:225-263
63. Joshi L, Murata Y, Wondisford FE, Szkudlinski MW, Desai R, Weintraub BD 1995 Recombinant TSH containing a β-subunit chimera with the human CG-β carboxy-terminus is biologically active, with a prolonged half-life: role of carbohydrate in bioactivity and metabolic clearance. Endocrinology 136:3839-3848
64. Grossmann M, Szkudlinski MW, Zeng H, Kraiem Z, Ji I, Tropea JE, Ji HT, Weintraub BD 1995 Role of the carboxy-terminal residues of the α-subunit in the expression and bioactivity of human thyroid-stimulating hormone. Mol Endocrinol 9:948-958
65. Morris III JC, Jiang N-S, Charlesworth MC, McCormick DJ, Ryan JR 1988 The effect of synthetic α-subunit peptides on thyrotropin interaction with its receptor. Endocrinology 123:456-46
66. Endo T, Tetsumoto T, Nagasaki H, Kashiwai T, Tamaki T, Amino N, Miyai K 1990 The distinct roles of α- and β-subunits of human thyrotropin in the receptor-binding and postreceptor events. Endocrinology 127:149-154
67. Clackson T, Wells JA 1995 A hot spot of binding energy in a hormone-receptor interface. Science 267:383-386
68. Wells JA 1996 Binding in the growth hormone receptor complex. Proc Natl Acad Sci USA 93:1-6
69. Szkudlinski MW, Teh NG, Grossmann M, Tropea JE, Witta J, Weintraub BD, Role of the 40-51 region of the alpha-subunit in the bioactivity of human thyrotropin, gonadotropins: implications for the design of new hormone analogs based on simultaneous mutagenesis of multiple domains. Program of the 10th International Congress of Endocrinology, San Francisco CA, 1996 (Abstract OR1-4)
70. Yun RH, Anderson A, Hermans J 1991 Proline in α-helix: stability and conformation studied by dynamics simulation. Proteins 10: 219-228
71. Ji I, Zeng H, Ji TH 1993 Receptor activation of and signal generation by the luteotropin/choriogonadotropin receptor. J Biol Chem 268: 22971-22974
72. Grossmann M, Szkudlinski MW, Dias JA, Xia H, Wong R, Puett D, Weintraub BD 1996 Site-directed mutagenesis of amino acids 33-44 of the common alpha-subunit reveals different structural requirements for heterodimer expression among the glycoprotein hormones and suggests that cAMP production and growth promotion are potentially dissociable functions of hTSH. Mol Endocrinol 10:769-779
73. Leinung MC, Reed DK, McCormick DJ, Ryan RJ, Morris JC 1991 Further characterization of the receptor-binding region of the thyroid-stimulating hormone α-subunit: a comprehensive synthetic peptide study of the α-subunit 26-46 sequence. Proc Natl Acad Sci USA 88:9707-9711
74. Grossmann M, Szkudlinski MW, Tropea JE, Bishop LA, Thotakura NR, Schofield PR, Weintraub BD 1995 Expression of human thyrotropin in cell lines with different glycosylation patterns combined with mutagenesis of specific glycosylation sites: characterization of a novel role for the oligosaccharides in the in vitro and in vivo bioactivity. J Biol Chem 270:29378-29385
75. Fares FA, Gruener N, Kraiem Z 1996 The role of the asparagine- linked oligosaccharides of the α-subunit in human thyrotropin bioactivity. Endocrinology 137:555-560
76. Cheng K-W, Glazer AN, Pierce JG 1973 The effects of modification of the COOH-terminal regions of bovine thyrotropin and its subunits. J Biol Chem 248:7930-7937
77. Parsons TF, Pierce JG 1979 Biologically active covalently cross- linked glycoprotein hormones and the effects of modification of the COOH-terminal region of their α-subunits. J Biol Chem 254:6010- 6015
78. 77a.Grossmann M, Szkudlinski MW, Weintraub BD, Generation of superactive human thyrotropin (hTSH) analogs by introduction of basic residues present in the human chorionic gonadotropin β-subunit. Program of the 79th Annual Meeting of The Endocrine Society, Minneapolis, MI, 1997 (Abstract OR1-5)
79. Grossmann M, Szkudlinski MW, Wong R, Dias JA, Ji TH, Weintraub BD 1997 Substitution of the seat-belt region of the thyrotropin (TSH)-β subunit with the corresponding regions of choriogonadotropin or follitropin confers luteotropic, but not follitropic, activity to chimeric TSH. J Biol Chem 272:15532-15540
80. Charlesworth MC, McCormick DJ, Madden B, Ryan RJ 1987 Inhibition of human choriotropin binding to receptor by human choriotropin α peptides. J Biol Chem 262:13409-13416
81. Keutmann HT, Charlesworth MR, Mason KA, Ostrea T, Johnson L, Ryan RJ 1987 A receptor-binding region on the human choriogonadotropin / lutropin β subunit. Proc Natl Acad Sci USA 84: 2038-2042
82. Matzuk MM, Keene JL, Boime I 1988 Site specificity of the chorionic gonadotropin N-linked oligosaccharides in signal transduction. J Biol Chem 264:2409-2414
83. Bielinska M, Boime I 1990 Site-directed mutagenesis identifies two receptor binding domains in the human chorionic gonadotropin alpha subunit. J Cell Biol 111:330a (Abstract 1844)
84. Campbell RK, Dean-Emig DM, Moyle WR 1991 Conversion of human choriogonadotropin into a follitropin by protein engineering. Proc Natl Acad Sci USA 88:760-764
85. Chen F, Wang Y, Puett D 1992 The carboxy-terminal region of the glycoprotein hormone α-subunit: contributions to receptor binding and signaling in human chorionic gonadotropin. Mol Endocrinol 6:914-919
86. Yoo J, Zeng H, Ji I, Murdoch WJ, Ji TH 1993 COOH-terminal amino acids of the α subunit play common and different roles in human choriogonadotropin and follitropin. J Biol Chem 268:13034- 13042
87. 44 in the human gonadotropin α-subunit. J Biol Chem 268:21613- 21617
88. Huang J, Ujihara M, Xia H, Chen F, Yoshida H, Puett D 1994 Mutagenesis of the 'determinant loop' region of human chorionic gonadotropin β. Mol Cell Endocrinol 90:211-218
89. Bishop LA, Robertson DM, Cahir N, Schofield PR 1994 Specific roles for the asparagine-linked carbohydrate residues of recombinant human follicle stimulating hormone in receptor binding and signal transduction. Mol Endocrinol 8:722-731
90. Flack MR, Froehlich J, Bennet AP, Anasti J, Nisula BC 1994 Site- directed mutagenesis defines the individual roles of the glycosylation sites on follicle-stimulating hormone. J Biol Chem 269:14015- 14020
91. Dias JA, Zhang Y, Liu X 1994 Receptor binding and functional properties of chimeric human follitropin prepared by an exchange between a small hydrophilic loop of human follitropin and human lutropin. J Biol Chem 269:25289-25294
92. Xia H, Puett D 1994 Identification of conserved amino acid residues in the β subunit of human choriogonadotropin important in holoprotein formation. J Biol Chem 269:17944-17953
93. Xia H, Chen F, Puett D 1994 A region in the human glycoprotein hormone α-subunit important in holoprotein formation and receptor binding. Endocrinology 134:1768-1770
94. 90 of the α-subunit are crucial for receptor binding and hormone action of follicle-stimulating hormone (FSH) and play hormone-specific roles in FSH and human chorionic gonadotropin. Endocrinology 136:2948-2953
95. Morris III JC, McCormick DJ, Ryan JR 1990 Inhibition of thyrotropin binding to receptor by synthetic human thyrotropin β peptides. J Biol Chem 265:1881-1884
96. Moyle WR, Campbell RK, Myers RV, Bernard MP, Han Y, Wang X 1994 Co-evolution of ligand-receptor pairs. Nature 368:251-255
97. Leinung MC, Bergert ER, McCormick DJ, Morris JC 1992 Synthetic analogs of the carboxyl-terminus of β-thyrotropin: the importance of basic amino acids in receptor binding activity. Biochemistry 31:10094-10098
98. Cosowsky L, Rao SN, Macdonald GJ, Papkoff H, Campbell RK, Moyle WR 1995 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 270:20011-20019
99. Moyle WR, Campbell RK, Rao SN, Ayad NG, Bernard MP, Han Y, Wang Y 1995 Model of human chorionic gonadotropin and lutropin receptor interaction that explains signal transduction of the glycoprotein hormones. J Biol Chem 270:20020-20031
100. Varki A 1993 Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97-130
101. Goochee CF, Monica T 1990 Environmental effects on protein glycosylation. Bio / Technology 8:421-427
102. Jenkins N, Parekh RB, James DC 1996 Getting the glycosylation right: implications for the biotechnology industry. Nat Biotechnol 14:975-981
103. Szkudlinski MW, Thotakura NR, Bucci I, Joshi LR, Tsai A, East- Palmer J, Shiloach J, Weintraub BD 1993 Purification and characterization of recombinant human thyrotropin (TSH) isoforms produced by Chinese hamster ovary cells: the role of sialylation and sulfation in TSH bioactivity. Endocrinology 133: 1490-1503
104. Elbein AD 1991 Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing. FASEB J 5:3055-3063
105. Fiedler K, Simons K 1995 The role of N-glycans in the secretory pathway. Cell 81:309-312
106. Weintraub BD, Stannard BS, Meyers L 1983 Glycosylation of thyroid- stimulating hormone in pituitary tumor cells: influence of high mannose oligosaccharide units on subunit aggregation, combination and intracellular degradation. Endocrinology 112:1331- 1345
107. Kaetzel DM, Virgin JB, Clay CM, Nilson JH 1989 Disruption of N-linked glycosylation of bovine luteinizing hormone beta-subunit by site-directed mutagenesis dramatically increases its intracellular stability but does not affect biological activity of the secreted heterodimer. Mol Endocrinol 3:1765-1774
108. Ruddon RW, Sherman SA, Bedows E 1996 Protein folding in the endoplasmatic reticulum: lessons from the human chorionic gonadotropin β subunit. Protein Sci 5:1443-1452
109. Sairam MR, Bhargavi GN 1985 A role for glycosylation of the α subunit in transduction of biological signal in glycoprotein hormones. Science 229:65-67
110. Amir SM, Kubota K, Tramontano D, Ingbar SH, Keutmann HT 1987 The carbohydrate moiety of bovine thyrotropin is essential for full bioactivity but not for receptor recognition. Endocrinology 120:345-352
111. Szkudlinski MW, Thotakura NR, Weintraub BD 1995 Subunit- specific functions of N-linked oligosaccharides in human thyrotropin: role of terminal residues of α- and β-subunit in metabolic clearance and bioactivity. Proc Natl Acad Sci USA 92:9062-9066
112. Moyle WR, Bahl OP, Maerz L 1974 Role of the carbohydrate of human chorionic gonadotropin in the mechanism of hormone action. J Biol Chem 250:9163-9169
113. Kalyan NK, Bahl OP 1983 Role of carbohydrate in human chorionic gonadotropin. J Biol Chem 258:67-74
114. Berman MI, Thomas CG, Manjunath P, Sairam MR, Nayfeh SN 1985 The role of the carbohydrate moiety in thyrotropin action. Biochem Biophys Res Commun 133:680-687
115. Nissim M, Lee K-O, Petrick PA, Dahlberg PA, Weintraub BD 1987 A sensitive thyrotropin (TSH) bioassay based on iodide uptake in rat FRTL- 5 thyroid cells: comparison with adenosine 3′,5′-monophosphate response to human serum TSH and enzymatically deglycosylated bovine and human TSH. Endocrinology 121:1278-1287
116. Papandreou MJ, Sergi I, Medri G, Labbe-Jullie C, Braun JM, Cannone C, Ronin C 1991 Differential effect of glycosylation on the expression of antigenic and bioactive domains in human thyrotropin. Mol Cell Endocrinol 78:137-150
117. 15N-enriched human chorionic gonadotropin. Biochemistry 35:8815-8823
118. Thotakura NR, LiCalzi L, Weintraub BD 1990 The role of carbohydrate in thyrotropin action assessed by a novel approach using enzymatic deglycosylation. J Biol Chem 265:11527-11534
119. Thotakura NR, Desai RK, Szkudlinski MW, Weintraub BD 1992 The role of the oligosaccharide chains of thyrotropin α- and β-subunits in hormone action. Endocrinology 141:82-88
120. Thotakura NR, Szkudlinski MW, Weintraub BD 1994 Structure- function studies of oligosaccharides of recombinant human thyrotropin by sequential deglycosylation and resialylation. Glycobiology 4:525-533
121. Calvo FO, Ryan RJ 1985 Inhibition of adenylyl activity in rat corpora luteal tissue by glycopeptides of human chorionic gonadotropin and the α-subunit of human chorionic gonadotropin. Biochemistry 24:1953-1959
122. Rebois RV, Liss MT 1987 Antibody binding to the beta-subunit of deglycosylated chorionic gonadotropin converts the antagonist to an agonist. J Biol Chem 262:3891-3896
123. Ji I, Ji TH 1990 Differential interactions of human choriogonadotropin and its aglycosylated analog with their receptor. Proc Natl Acad Sci USA 87:4396-4400
124. Schwarz S, Krude H, Merz WE, Lottersberger C, Wick G, Berger P 1991 Epitope mapping of the receptor-bound agonistic form of human chorionic gonadotropin (hCG) in comparison to the antagonistic form (deglycosylated hCG). Biochem Biophys Res Commun 178:699-706
125. Grossmann M, Wong R, Teh NG, Tropea JE, East-Palmer J, Weintraub BD, Szkudlinski MW 1997 Expression of biologically active human thyrotropin (hTSH) in a baculovirus system: effect of insect cell glycosylation on hTSH activity in vitro and in vivo. Endocrinology 138:92-100
126. Keene JL, Matzuk MM, Boime I 1989 Expression of recombinant chorionic gonadotropin in Chinese hamster ovary glycosylation mutants. Mol Endocrinol 3:2011-2017
127. Galway AB, Hsueh AJW, Keene JL, Yamoto M, Fauser BCJM, Boime I 1990 In vitro and in vivo bioactivity of human follicle- stimulating hormone and partially deglycosylated variants secreted by transfected eukaryotic cell lines. Endocrinology 127:93- 100
128. Thotakura NR, Desai RK, Bates LG, Cole ES, Pratt BM, Weintraub BD 1991 Biological activity and metabolic clearance of a recombinant human thyrotropin produced in Chinese hamster ovary cells. Endocrinology 128:341-348
129. Smith PL, Kaetzel D, Nilson J, Baenziger JU 1990 The sialylated oligosaccharides of recombinant bovine lutropin modulate hormone bioactivity. J Biol Chem 265:874-881
130. Bishop LA, Nguyen TV, Schofield PR 1995 Both of the β-subunit carbohydrate residues of follicle-stimulating hormone determine the metabolic clearance rate and in vivo potency. Endocrinology 136:2635-2640
131. Szkudlinski MW, Thotakura NR, Tropea JE, Grossmann M, Weintraub BD 1995 Asparagine-linked oligosaccharide structures determine clearance and organ distribution of pituitary and recombinant thyrotropins (TSH). Endocrinology 136:3325- 3330
132. Kidd M, Emery VC 1993 The use of baculoviruses as expression vectors. Appl Biochem Biotechnol 42:137-155
133. Luckow VA 1993 Baculovirus system for the expression of human gene products. Curr Opin Biotechnol 4:564-572
134. Chen W, Shen QY, Bahl OP 1991 Carbohydrate variant of the recombinant β-subunit of human choriogonadotropin expressed in baculovirus expression system. J Biol Chem 266:4081-4087
135. Braisted AC, Wells JA 1996 Minimizing a binding domain from protein A. Proc Natl Acad Sci USA 93:5688-5682
136. Shao Z, Arnold FH 1996 Engineering new functions and altering existing functions. Curr Opin Struct Biol 6:513-518
137. Hsueh AJW, LaPolt P 1992 Molecular basis of gonadotropin receptor regulation. Trends Endocrinol Metab 3:164-170
138. Kobe B, Deisenhofer J 1995 Proteins with leucine-rich repeats. Curr Opin Struct Biol 5:409-416
139. Kajava AV, Vassart G, Wodak SJ 1995 Modeling of the three- dimensional structure of proteins with the typical leucine-rich repeats. Structure 3:867-877
140. Jiang X, Dreano M, Buckler DR, Cheng S, Ythier A, Wu H, Hendrickson WA, Tayar NE 1995 Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions. Structure 3:1341- 1353
141. Bhomwick N, Huang J, Puett D, Isaacs NW, Lapthorn AJ 1996 Determination of residues important in hormone binding to the extracellular domain of the luteinizing hormone / chorionic gonadotropin receptor by site- directed mutagenesis and modeling. Mol Endocrinol 10:1147-1159
142. Pantel J, Remy J-J, Salesse R, Jolivet A, Bidart J-M 1993 Unmasking of an immunoreactive site on the α subunit of human choriogonadotropin bound to the extracellular domain of its receptor. Biochem Biophys Res Commun 195:588-593
143. Chazenbalk GD, Rapoport B 1995 Expression of the extracellular domain of the thyrotropin receptor in the baculovirus system using a promoter active earlier than the polyhedrin promoter. Implications for the expression of functional highly glycosylated proteins. J Biol Chem 270:1543-1549
144. Strader CD, Fong TM, Tota MR, Underwood D 1994 Structure and function of G protein-coupled receptors. Annu Rev Biochem 63: 101-132
145. Hoflack J, Hibert MF, Trumpp-Kallmeyer S 1993 Three-dimensional models of gonadothyrotropin hormone receptor transmembrane domain. Drug Des Discov 10:157-171
146. Kundu GC, Ji I, McCormick DJ, Tae HT 1996 Photoaffinity labeling of the lutropin receptor with synthetic peptide for carboxyl terminus of the human choriogonadotropin α subunit. J Biol Chem 271:11063-11066
147. Remy JJ, Bozon V, Couture L, Goxe B, Salesse R, Garnier J 1993 Reconstitution of a high-affinity functional lutropin receptor by coexpression of its extracellular and membrane domains. Biochem Biophys Res Commun 193:1023-1030
148. Ji I, Ji TH 1990 Human choriogonadotropin binds to a lutropin receptor with essentially no N-terminal extension and stimulates cAMP synthesis. J Biol Chem 266:13076-13079
149. Paschke R, Parmentier M, Vassart G 1994 Importance of the extracellular domain of the human thyrotropin receptor for activation of cyclic AMP production. J Mol Endocrinol 13:199-207
150. Gilman AG 1987 G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56:615-634
151. Rapoport B, Spaulding SW 1996 Mechanism of action of thyrotropin and other thyroid growth factors. In: Braverman LE, Utiger RD (eds) Werner and Ingbars' The Thyroid. Lippincott-Raven, Philadelphia, pp 207-219
152. Van Sande J, Parma J, Tonacchera M, Swillens S, Dumont J, Vassart G 1995 Somatic and germline mutations of the TSH receptor gene in thyroid diseases. J Clin Endocrinol Metab 80:2577- 2585
153. Chazenbalk GD, Kakinuma A, Jaume JC, McLachlan SM, Rapoport B 1996 Evidence of negative cooperativity among human thyrotropin receptors overexpressed in mammalian cells. Endocrinology 137:4586-4591
154. Ostrowski J, Kjelsberg MA, Caron MG, Lefkowitz RJ 1992 Mutagenesis of the β2-adrenergic receptor: how structure elucidates function. Annu Rev Pharmacol Toxicol 32:167-183
155. Stein SA, Oates EL, Hall CR, Grumbles RM, Fernandez LM, Taylor NA, Puett D, Jin S 1994 Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol 8:129-138
156. Refetoff S, Sunthornthepvarakul T, Gottschalk ME, Hayashi Y 1996 Resistance to thyrotropin and other abnormalities of the thyrotropin receptor. Recent Prog Horm Res 51:97-120
157. 4-4GalNAcβ1, 4GlcNACβ1, 2Manα that mediates rapid clearance of lutropin. Cell 67:1103-1110
158. Drickhamer K 1991 Clearing up glycoprotein hormones. Cell 67: 1029-1032
159. Ashwell G, Harford J 1982 Carbohydrate-specific receptors in the liver. Annu Rev Biochem 51:531-554
160. Gesundheit N, Weintraub BD 1986 Mechanisms and regulation of TSH glycosylation. Adv Exp Med Biol 205:87-105
161. Miura Y, Perkel VS, Papenberg KA, Johnson MJ, Magner JA 1989 Concanavalin-A, lentil, and ricin lectin affinity binding characteristics of human thyrotropin: differences in the sialylation of thyrotropin in sera of euthyroid, primary and central hypothyroid patients. J Clin Endocrinol Metab 69:985-995
162. Papandreou MJ, Persani L, Asteria Ronin C, Beck-Peccoz P 1993 Variable carbohydrate structures of circulating thyrotropin as studied by lectin affinity chromatography in different clinical conditions. J Clin Endocrinol Metab 77:393-398
163. Beck-Peccoz P, Persani L 1994 Variable biological activity of thyroid- stimulating hormone (TSH). Eur J Endocrinol 130:331- 340
164. Beck-Peccoz P, Amr S, Menzes-Ferreira M, Faglia G, Weintraub BD 1985
165. Lee KO, Persani L, Tan M, Sundram FX, Beck-Peccoz P 1995 Thyrotropin with decreased biological activity, a delayed consequence of cranial irradiation for nasopharyngeal carcinoma. J Endocrinol Invest 18:800-805
166. Helton TE, Magner JA 1994 Sialyltransferase messenger ribonucleic acid increases in thyrotrophs of hypothyroid mice: an in situ hybridization study. Endocrinology 134:2347-2353
167. Helton TE, Magner JA 1995 Beta-galactoside alpha-2,3-sialyltransferase messenger RNA increases in thyrotrophs of hypothyroid mice. Thyroid 5:315-317
168. Dharmesh SM, Baenziger JU 1993 Estrogen modulates expression of the glycosyltransferases that synthesize sulfated oligosaccharides of lutropin. Proc Natl Acad Sci USA 90:11127-11131
169. Hayashizaki Y, Hiraoka Y, Endo Y, Matsubara K 1989 Thyroid- stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the β-subunit. EMBO J 8:2291- 2296
170. Dacou-Voutetakis C, Feltquate DM, Drakopoulou M, Kourides IA, Dracopoli NC 1990 Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone β-subunit gene. Am J Hum Genet 46:988-993
171. Medeiros-Neto G, Herodotou DT, Rajan S, Kommareddi S, de Lacerda L, Sandrini R, Boguszewski MCS, Hollenberg AN, Radovick S, Wondisford FE 1996 A circulating biologically inactive thyrotropin caused by a mutation in the beta subunit gene. J Clin Invest 97:1250-1256
172. Matthews CH, Borgato S, Beck-Peccoz P, Adams M, Tone Y, Gambino G, Casagrande G, Tedeschini G, Benedetti A, Chatterjee VKK 1993 Primary amenorrhoea and infertility due to a mutation in the β-subunit gene of follicle-stimulating hormone. Nat Genet 5:83-86
173. Weiss J, Axelrod L, Whitcomb RW, Harris PE, Crowley WF, Jameson JL 1992 Hypogonadism caused by a single amino acid substitution in the beta subunit of luteinizing hormone. N Engl J Med 326:179-183
174. Bo M, Boime I 1992 Identification of the transcriptionally active genes of the chorionic gonadotropin beta gene cluster in vivo. J Biol Chem 267:3179-3184
175. Suganuma N, Matzuk MM, Boime I 1989 Elimination of disulfide bonds affects assembly and secretion of the human chorionic gonadotropin beta subunit. J Biol Chem 264:19302-19307
176. Raivio T, Huhtaniemi I, Anttila R, Simes MA, Hagenäs L, Nilsson C, Petterson K, Dunkel L 1996 The role of luteinizing hormone-β gene polymorphism in the onset and progression of puberty in healthy boys. J Clin Endocrinol Metab 81:3279-3282
177. Suganuma N, Furui K, Kikkawa F, Tomoda Y, Furuhashi M 1996 Effects of the mutations (Trp8-Arg and Ile15-Thr) in human luteinizing hormone (LH) β-subunit on LH bioactivity in vitro and in vivo. Endocrinology 137:831-838
178. Fradkin JE, Eastman RC, Lesniak MA, Roth J 1989 Specificity spillover at the hormone receptor-exploring its role in human disease. N Engl J Med 320:640-645
179. Mann K, Hoermann R 1993 Thyroid stimulation by placental factors. J Endocrinol Invest 16, 378-384
180. Yoshimura M, Hershman JM 1995 Thyrotropic action of human chorionic gonadotropin. Thyroid 5:425-434
181. Tomer Y, Huber GK, Davies TF 1992 Human chorionic gonadotropin (hCG) interacts directly with recombinant human TSH receptors. J Clin Endocrinol Metab 74:1477-1479
182. Yoshimura M, Hershman JM, Pang XP, Berg L, Pekary AE 1993 Activation of the thyrotropin (TSH) receptor by human chorionic gonadotropin and luteinizing hormone in Chinese hamster ovary cells expressing functional human TSH receptors. J Clin Endocrinol Metab 77:1009-1013
183. Hoermann R, Broecker M, Grossmann M, Mann K, Derwahl M 1994 Interaction of human chorionic gonadotropin (hCG) and asialo-hCG with recombinant human thyrotropin receptor. J Clin Endocrinol Metab 78:933-938
184. Carayon P, Amr S, Nisula BC, Lissitzky S 1981 Effect of carboxypepridase digestion of the human chorionic gonadotropin molecule on its thyrotropic activity. Endocrinology 108:1891-1898
185. Kendle F 1905 Case of precocious puberty in a female cretin. Br Med J 1:246-248
186. Barnes ND, Hayles AB, Ryan RJ 1973 Sexual maturation in juvenile hypothyroidism. Mayo Clin Proc 48:849-856
187. Anasti JN, Flack MR, Froehlich J, Nelson LM, Nisula BC 1995 A potential novel mechanism for precocious puberty in juvenile hypothyroidism. J Clin Endocrinol Metab 80:276-279
188. Hidaka A, Ban T, Panesar NS, Minigeshi T, Kohn LD, Tahara K 1994 Thyrotropin stimulation of the lutropin / gonadotropin receptor: different sites mediate agonist activity and high affinity binding. Thyroid 4:447-457
189. Nagayama Y, Yamasaki H, Takeshita A, Kimura H, Ashizawa K, Yokoyama N, Yamashita S, Rapoport B, Nagataki S 1995 Thyrotropin binding specificity for the thyrotropin receptor. J Endocrinol Invest 18:283-287
190. Navarro C, Corretger J, Sancho A, Rovira J, Morales L 1985 Paraneoplastic precocious puberty. Cancer 56:1725-1729
191. Jannini EA, Ulisse S, d'Armiento M 1995 Thyroid hormone and male gonadal function. Endocr Rev 16:443-459
192. Tian Y, Wu L-H, Oxender DL, Chung F-Z 1996 The unpredicted high affinities for a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity. J Biol Chem 271:20250- 20257
193. Strickland TW, Puett D 1982 Alpha-subunit conformation in glycoprotein hormones and recombinants as assessed by specific antisera. Endocrinology 111:95-100
194. Hojo H, Ryan RJ 1985 Monoclonal antibodies against human follicle- stimulating hormone. Endocrinology 117:2428-2434
195. Weiner RS, Dias JA 1992 Biochemical analyses of proteolytic nicking of the human glycoprotein hormone alpha-subunit and its effect on conformational epitopes. Endocrinology 131:1026- 1036
196. Rapoport B, Takai NA, Filetti S 1982 Evidence for species specificity in the interaction between thyrotropin and thyroid-stimulating immunoglobulin and their receptor in thyroid tissue. J Clin Endocrinol Metab 54:1059-1062
197. East-Palmer J, Szkudlinski MW, Lee J, Thotakura NR, Weintraub BD 1995 A novel nonradioactive in vivo bioassay of thyrotropin (TSH). Thyroid 5:55-59
198. Condliffe PG, Weintraub BD 1979 Pituitary thyroid-stimulating hormone and other thyroid stimulating substances. In: Gray CH, James VHT (eds) Hormones in Blood, ed 3. Academic Press, New York, pp 499-574
199. Tullner WW 1994 Comparative aspects of primate chorionic gonadotropins. Contrib Primat 3:235-257
200. Turner RC, Levy JC, Clark A 1993 Complex genetics of the type 2 diabetes: thrifty genes and previously neutral polymorphisms. QJM 86:413-417
201. Wallis M 1994 Variable evolutionary rates in the molecular evolution of mammalian growth hormones. J Mol Evol 38:619- 627
202. 131) in the postoperative treatment of thyroid cancer. Cancer 13:745-756
203. Braverman LE, Pratt BM, Ebner S, Longcope C 1992 Recombinant human thyrotropin stimulates thyroid function and radioactive iodine uptake in the Rhesus monkey. J Clin Endocrinol Metab 74:1135-1139
204. McPherson JM, Livingston DJ 1989 Protein engineering: new approaches to improved therapeutic proteins, part III. Pharmacol Technol 9:32-42
205. Recombinant Human FSH Study Group 1995 Clinical assessment of recombinant human follicle-stimulating hormone before in vitro fertilization. Fertil Steril 63:77-86
206. Fares FA, Suganuma N, Nishimori K, LaPolt PS, Hsueh AJW, Boime I 1992 Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin β subunit to the follitropin β subunit. Proc Natl Acad Sci USA 89: 4304-4308
207. LaPolt PS, Nishimori K, Fares FA, Perlas E, Boime I, Hsueh AJW 1992 Enhanced stimulation of follicle maturation and ovulatory potential by long acting follicle-stimulating hormone agonists with extended carboxyl-terminal peptides. Endocrinology 131: 2514-2520
208. Furuhashi M, Shikone T, Fares FA, Sugahara T, Hsueh AJW, Boime I 1995 Fusing the carboxyterminal peptide of the chorionic gonadotropin (CG) β-subunit to the common α-subunit: retention of O-linked glycosylation and enhanced in vivo bioactivity of chimeric human CG. Mol Endocrinol 9:54-63
209. Sugahara T, Pixley MR, Minami S, Perlas E, Ben-Menahem D, Hsueh AJW, Boime I 1995 Biosynthesis of a biologically active single peptide chain containing the common α and chorionic gonadotropin β subunits in tandem. Proc Natl Acad Sci USA 92: 2041-2045
210. Narayan P, Wu C, Puett D 1995 Functional expression of yoked human chorionic gonadotropin in baculovirus-infected insect cells. Mol Endocrinol 9:1720-1726
211. Ben-Menahem D, Boime I 1996 Converting heterodimeric gonadotropins to genetically linked single chains. Trends Endocrinol Metab 7:100-105
212. 210a.Grossmann M, Wong R, Szkudlinski MW, Weintraub BD 1997 Human thyroid-stimulating hormone (hTSH) subunit gene fusion produces hTSH with increased stability and serum half-life and compensates for mutagenesis-induced defects in subunit association. J Biol Chem, in press
213. Leitolf H, Szkudlinski MW, Hoang-Vu C, Thotakura NR, von zur Muhlen A, Brabant G, Weintraub BD 1995 Effects of continuous, pulsatile administration of pituitary rat thyrotropin and recombinant human thyrotropin in a chronically cannulated rat. Horm Metab Res 27:173-178
214. Bahn RS, Heufelder AE 1993 Pathogenesis of Graves' ophthalmopathy. N Engl J Med 329:1468-1475
215. Davies TF 1994 Editorial: The thyrotropin receptors spread themselves around. J Clin Endocrinol Metab 79:1232-1233
216. Paschke R, Vassart G, Ludgate M 1995 Current evidence for and against TSH receptor being the common antigen in Graves' disease and thyroid associated ophthalmopathy. Clin Endocrinol (Oxf) 42:565-569
217. Hoermann R, Schumm-Draeger PM, Rehbach K, Mann K 1991 Asialoagalacto-human chorionic gonadotropin, a carbohydrate- modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo. J Clin Invest 88:1947-1954
218. Hassoun AAK, Bergert ER, Morris JC, Development of TSH antagonists. Program of the 77th Annual Meeting of The Endocrine Society, Washington DC, 1995, p 47 (Abstract)
219. Pekonen F, Weintraub BD 1978 Thyrotropin binding to cultured lymphocytes and thyroid cells. Endocrinology 103:1668-1672
220. Mullin BR, Lee G, Ledley FD, Minland RJ, Kohn LD 1976 Thyrotropin interactions with human fat cell membrane preparations and the finding of soluble thyrotropin binding component. Biochem Biophys Res Commun 65:55-62
221. Trokoudes KM, Sugenoya A, Hazani E, Row W, Volpe R 1979 Thyroid-stimulating hormone (TSH) binding to extracellular human thyroid tissues: TSH and thyroid-stimulating immunoglobulin effect on adenosine 3′,5′-monophosphate in testicular and adrenal tissues. J Clin Endocrinol Metab 48:919-923
222. Takeshita A, Nagayama Y, Fujiyama K, Yokoyama N, Namba H, Yamashita S, Izumi M, Nagataki S 1992 Molecular cloning and sequencing of an alternatively spliced form of human thyrotropin receptor transcript. Biochem Biophys Res Commun 188: 1214-1219
223. Peele ME, Carr FE, Baker JR, Wartofsky L, Burman KD 1993 TSH beta subunit gene expression in human lymphocytes. Am J Med Sci 305:1-7
224. Provinciali M, Di Stefano G, Fabris N 1992 Improvement of proliferative capacity and natural killer cell activity of murine spleen lymphocytes by thyrotropin. Int J Immunopharmacol 14:865-870
225. Endo T, Ohta K, Haraguchi K, Onaya T 1995 Cloning and functional expression of thyrotropin receptor cDNA from fat cells. J Biol Chem 270:10833-10837
226. Marcus C, Ehren H, Arner P 1988 Regulation of lipolysis during the neonatal period: importance of thyrotropin. J Clin Invest 82:1793- 1797
227. Pabon JE, Bird JS, Li X, Huang Z-H, Lei ZM, Sanfilippo JS, Yussman MA, Rao CV 1996 Human skin contains luteinizing hormone / chorionic gonadotropin receptors. J Clin Endocrinol Metab 81:2738-2741
228. Ghinea N, Hai MTV, Groyer-Picard MT, Milgrom E 1994 How protein hormones reach their target cells. Receptor-mediated transcytosis of hCG through endothelial cells. J Cell Biol 125: 87-97
229. Birken S, Maydelman Y, Gawinowicz MA, Pound A, Liu Y, Stockell Hartree A 1996 Isolation of human pituitary chorionic gonadotropin. Endocrinology 137:1402-1411
230. Grossmann M, Trautmann ME, Poertl S, Hoermann R, Berger P, Arnold R, Mann K 1994 Alpha-subunit and human chorionic gonadotropin-β immunoreactivity in patients with malignant endocrine gastroenteropancreatic tumours. Eur J Clin Invest 24: 131-136
231. Grossmann M, Hoermann R, Gocze PM, Ott M, Berger P, Mann K 1995 Measurement of human chorionic gonadotropin-related immunoreactivity in serum, ascites and tumor cysts of patients with gynaecologic malignancies. Eur J Clin Invest 25:867- 873
232. Carrel DT, Hammond ME, Odell WD 1993 Evidence for an autocrine / paracrine function of chorionic gonadotropin in Xanthomonas maltophilia. Endocrinology 132:1085-1089
233. Thotakura NR, Blithe DL 1995 Glycoprotein hormones: glycobiology of gonadotropins, thyrotropin and free α subunit. Glycobiology 5:3-10
234. Gill PS, Lunardi-Iskandar Y, Louie S, Tulpule A, Zheng T, Espina BM, Besnier JM, Hermans P, Levine AM, Bryant JL, Gallo RC 1996 The effects of preparations of human chorionic gonadotropin on AIDS-related Kaposi's sarcoma. N Engl J Med 335:1261-1269
235. Murray-Rust J, McDonald NQ, Blundell TL, Hosnag M, Oefner C, Winkler F, Bradshow RA 1993 Topological similarities in TGF β2, PDGF-BB and NGF define a superfamily of polypeptide growth factors. Structure 1:153-159
236. Kyte J 1995 Evolution. In: Structure in Protein Chemistry. Garland Publishing, Inc., New York, pp 243-279
237. Ryden M, Murray-Rust J, Glass D, Ilag LL, Trupp M, Yancopoulos GD, McDonald NQ, Ibanez CF 1995 Functional analysis of mutant neurotrophins deficient in low affinity binding reveals a role for p75LNGFR in NT-4 signaling. EMBO J 14:1979-1990
238. Griffith DL, Keck PC, Kuber Sampath T, Rueger DC, Carlson WD 1996 Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor β superfamily. Proc Natl Acad Sci USA 93:878-883