The biology of activin: Recent advances in structure, regulation and function

Journal of Endocrinology

Volumn 202, Issue 1, 2009, Pages 1-12

  Xia, Yin ^a   Schneyer, Alan L ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MASSACHUSETTS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN; ACTIVIN RECEPTOR 1; ACTIVIN RECEPTOR 2; FOLLISTATIN; FOLLITROPIN BETA SUBUNIT; GONADORELIN; INHIBIN; LUTEINIZING HORMONE BETA SUBUNIT; MYOSTATIN;

BINDING AFFINITY; BINDING SITE; BIOLOGICAL ACTIVITY; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL TYPE; CRYSTAL STRUCTURE; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; GLUCOSE METABOLISM; GONAD DEVELOPMENT; HUMAN; HYPOPHYSIS FUNCTION; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; INSULIN RELEASE; LUTEOLYSIS; NONHUMAN; OVARY FOLLICLE DEVELOPMENT; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS REGULATION; REPRODUCTION; REVIEW; SEX DIFFERENTIATION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; TESTIS FUNCTION; ANIMAL; CHEMISTRY; FEMALE; GENDER AND SEX; GENE EXPRESSION REGULATION; GENETICS; MALE; METABOLISM; OVARY FOLLICLE; PHYSIOLOGY; STEM CELL; TESTIS;

ACTIVINS; ANIMALS; FEMALE; GENE EXPRESSION REGULATION; HUMANS; LUTEOLYSIS; MALE; OVARIAN FOLLICLE; SEX DETERMINATION (GENETICS); STEM CELLS; STRUCTURE-ACTIVITY RELATIONSHIP; TESTIS;

EID: 67650717476     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1677/JOE-08-0549     Document Type: Review

References (153)

1. Abe M, Shintani Y, Eto Y, Harada K, Kosaka M & Matsumoto T 2002 Potent induction of activin A secretion from monocytes and bone marrow stromal fibroblasts by cognate interaction with activated T cells. Journal of Leukocyte Biology 72 347-352.
2. Allendorph GP, Vale WW & Choe S 2006 Structure of the ternary signaling complex of a TGF-beta superfamily member. PNAS 103 7643-7648.
3. Anasti JN 1998 Premature ovarian failure: an update. Fertility and Sterility 70 1-15.
4. Antenos M, Stemler M, Boime I & Woodruff TK 2007 N-linked oligosaccharides direct the differential assembly and secretion of inhibin alpha- and betaA-subunit dimers. Molecular Endocrinology 21 1670-1684.
5. Antenos M, Zhu J, Jetly NM & Woodruff TK 2008 An activin/furin regulatory loop modulates the processing and secretion of inhibin α- and βB-subunit dimers in pituitary gonadotrope cells. Journal of Biological Chemistry 283 33059-33068.
6. Bailey JS, Rave-Harel N, McGillivray SM, Coss D & Mellon PL 2004 Activin regulation of the follicle-stimulating hormone beta-subunit gene involves Smads and the TALE homeodomain proteins Pbx1 and Prep1. Molecular Endocrinology 18 1158-1170.
7. Beattie GM, Lopez AD, Bucay N, Hinton A, Firpo MT, King CC & Hayek A 2005 Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells 23 489-495.
8. Bernard DJ 2004 Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone beta subunit in mouse gonadotrope cells. Molecular Endocrinology 18 606-623.
9. Bertolino P, Holmberg R, Reissmann E, Andersson O, Berggren PO & Ibáñez CF 2008 Activin B receptor ALK7 is a negative regulator of pancreatic beta-cell function. PNAS 105 7246-7251.
10. Bhushan A, Chen Y & ValeW1998 Smad7 inhibits mesoderm formation and promotes neural cell fate in Xenopus embryos. Developmental Biology 200 260-268.
11. Bingham EL, Cheng SP, Ignatoski KW & Doherty GM 2008 Differentiation of hES cells to a parathyroid-like phenotype. Stem Cells and Development (in press: DOI 10.1089/3cd-2008.0337).
12. Bonner-Weir S 1994 Regulation of pancreatic beta-cell mass in vivo. Recent Progress in Hormone Research 49 91-104.
13. Bristol-Gould S, Kreeger P, Selkirk C, Kilen S, Cook R, Kipp J, Shea LD, Mayo KE & Woodruff TK 2006 Postnatal regulation of germ cells by activin: the establishment of the initial follicle pool. Developmental Biology 80 132-148.
14. Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA et al. 2007 Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448 191-195.
15. Brown CW, Houston-Hawkins DE, Woodruff TK & Matzuk MM 2000 Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Nature Genetics 25 453-457.
16. Brun T, Franklin I, St-Onge L, Biason-Lauber A, Schoenle EJ, Wollheim CB & Gauthier BR 2004 The diabetes-linked transcription factor PAX4 promotes β-cell proliferation and survival in rat and human islets. Journal of Cell Biology 167 1123-1135.
17. Buzzard JJ, Farnworth PG, de Kretser DM, O'Connor AE, Wreford NG & Morrison JR 2003 Proliferative phase sertoli cells display a developmentally regulated response to activin in vitro. Endocrinology 144 474-483.
18. Cherrington BD, Farmerie TA, Lents CA, Cantlon JD, Roberson MS & Clay CM 2005 Activin responsiveness of the murine gonadotropin-releasing hormone receptor gene is mediated by a composite enhancer containing spatially distinct regulatory elements. Molecular Endocrinology 19 898-912.
19. Cho SH, Yao Z, Wang SW, Alban RF, Barbers RG, French SW & Oh CK 2003 Regulation of activin A expression in mast cells and asthma: its effect on the proliferation of human airway smooth muscle cells. Journal of Immunology 170 4045-4052.
20. Coss D, Thackray VG, Deng CX & Mellon PL 2005 Activin regulates luteinizing hormone beta-subunit gene expression through Smad-binding and homeobox elements. Molecular Endocrinology 19 2610-2623.
21. Coutts SM, Childs AJ, Fulton N, Collins C, Bayne RAL, McNeilly AS & Anderson RA 2008 Activin signals via SMAD2/3 between germ and somatic cells in the human fetal ovary and regulates kit ligand expression. Developmental Biology 314 189-199.
22. DePaolo LV 1997 Inhibins, activins, and follistatins: the saga continues. Proceedings of the Society for Experimental Biology and Medicine 214 328-339.
23. Ebert S, ZeretzkeM, Nau R & Michel U 2007 Microglial cells and peritoneal macrophages release activin A upon stimulation with Toll-like receptor agonists. Neuroscience Letters 413 241-244.
24. Eramaa M, Hurme M, Stenman UH & Ritvos O 1992 Activin A/erythroid differentiation factor is induced during human monocyte activation. Journal of Experimental Medicine 176 1449-1452.
25. Erickson GF & Shimasaki S 2003 The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reproductive Biology and Endocrinology 1 9.
26. Florio P, Luisi S, Marchetti P, Lupi R, Cobellis L, Falaschi C, Sugino H, Navalesi R, Genazzani AR & Petraglia F 2000 Activin A stimulates insulin secretion in cultured human pancreatic islets. Journal of Endocrinological Investigation 23 231-234.
27. Frandsen U, Porneki AD, Floridon C,Abdallah BM & Kassem M 2007 Activin B mediated induction of Pdx1 in human embryonic stemcell derived embryoid bodies. Biochemical and Biophysical Research Communications 362 568-574.
28. Fumagalli M, Musso T, VermiW, Scutera S, Daniele R, Alotto D, Cambieri I, Ostorero A, Gentili F, Caposio P et al. 2007 Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin. Experimental Dermatology 16 600-610.
29. Funa NS, Saldeen J, Akerblom B & Welsh M 2008 Interdependent fibroblast growth factor and activin A signaling promotes the expression of endodermal genes in differentiating mouse embryonic stem cells expressing Src homology 2-domain inactive Shb. Differentiation 76 443-453.
30. Funaba M, Ikeda T, Ogawa K,MurakamiM& AbeM2003 Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration. Journal of Leukocyte Biology 73 793-801.
31. Furukawa M, Nobusawa R, Shibata H, Eto Y & Kojima I 1995 Initiation of insulin secretion in glucose-free medium by activin A. Molecular and Cellular Endocrinology 113 83-87.
32. Glister C, Groome NP & Knight PG 2006 Bovine follicle development is associated with divergent changes in activin-A, inhibin-A and follistatin and the relative abundance of different follistatin isoforms in follicular fluid. Journal of Endocrinology 188 215-225.
33. Gould SE, Day M, Jones SS & Dorai H 2002 BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells1. Kidney International 61 51-60.
34. Greenwald J, Vega ME, Allendorph GP, Fischer WH, ValeW& Choe S 2004 A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors. Molecular Cell 15 485-489.
35. Gregory SJ & Kaiser UB 2004 Regulation of gonadotropins by inhibin and activin. Seminars in Reproductive Medicine 22 253-267.
36. Gregory SJ, Lacza CT, Detz AA, Xu S, Petrillo LA & Kaiser UB 2004 Synergy between activin A and GnRH in transcriptional activation of the rat follicle-stimulating hormone beta (FSHb) gene. Molecular Endocrinology 19 237-254.
37. Griffith DL, Keck PC, Sampath TK, Rueger DC & CarlsonWD1996 Threedimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily. PNAS 93 878-883.
38. Guo Q, Kumar TR, Woodruff TW, Hadsell LA, DeMayo FJ & Matzuk MM 1998 Overexpression of mouse follistatin causes reproductive defects in transgenic mice. Molecular Endocrinology 12 96-106.
39. Hagen M, Fagan K, Steudel W, Carr M, Lane K, Rodman DM & West J 2007 Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. American Journal of Physiology. Lung Cellular and Molecular Physiology 292 L1473-L1479.
40. Hay DC, Fletcher J, Payne C, Terrace JD, Gallagher RC, Snoeys J, Black JR, Wojtacha D, Samuel K, Hannoun Z et al. 2008 Highly efficient differentiation of hESCs to functional hepatic endoderm requires activin A and Wnt3a signaling. PNAS 105 12301-12306.
41. Hinck AP, Archer SJ, Qian SW, Roberts AB, Sporn MB, Weatherbee JA, Tsang MLS, Lucas R, Zhang BL,Wenker J et al. 1996 Transforming growth factor beta 1: three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor beta 2. Biochemistry 35 8517-8534.
42. Hubner G, Hu Q, Smola H & Werner S 1996 Strong induction of activin expression after injury suggests an important role of activin in wound repair. Developmental Biology 173 490-498.
43. Hubner G, Alzheimer C & Werner S 1999 Activin: a novel player in tissue repair processes. Histology and Histopathology 14 295-304.
44. Jafary H, Larijani B, Farrokhi A, Pirouz M, Mollamohammadi S & Baharvand H 2008 Differential effect of activin onmouse embryonic stemcell differentiation in insulin-secreting cells under nestin-positive selection and spontaneous differentiation protocols. Cell Biology International 32 278-286.
45. James D, Levine AJ, Besser D & Hemmati-Brivanlou A 2005 TGFbeta/ activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132 1273-1282.
46. Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G & Majumdar AS 2007 Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25 1940-1953.
47. Jones KL, de Kretser DM, Clarke IJ, Scheerlinck JP & Phillips DJ 2004 a Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe. Journal of Endocrinology 182 69-80.
48. Jones KL, Kretser DM, Patella S & Phillips DJ 2004b Activin A and follistatin in systemic inflammation. Molecular and Cellular Endocrinology 225 119-125.
49. Jones KL, Mansell A, Patella S, Scott BJ, Hedger MP, de Kretser DM & Phillips DJ 2007 Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia. PNAS 104 16239-16244.
50. Jorgez CJ, Klysik M, Jamin SP, Behringer RR & Matzuk MM 2003 Granulosa cell-specific inactivation of follistatin causes female fertility defects. Molecular Endocrinology 18 953-967.
51. Kaitu'u-Lino TJ, Phillips DJ,Morison NB & Salamonsen LA 2008 A new role for activin in endometrial repair after menses. Endocrinology (in press: DOI 10.1210/en.2008-0738).
52. Kelber JA, Shani G, Booker EC, Vale WW & Gray PC 2008 Cripto is a noncompetitive activin antagonist that forms analogous signaling complexes with activin and nodal. Journal of Biological Chemistry 283 4490-4500.
53. Keutmann HT, Schneyer AL & Sidis Y 2004 The role of follistatin domains in follistatin biological action. Molecular Endocrinology 18 228-240.
54. Kipp JL, Kilen SM, Woodruff TK & Mayo KE 2007 Activin regulates estrogen receptor gene expression in the mouse ovary. Journal of Biological Chemistry 282 36755-36765.
55. Kitamura R, Takahashi T, Nakajima N, Isodono K, Asada S, Ueno H, Ueyama T, Yoshikawa T, Matsubara H & Oh H 2007 Stage-specific role of endogenous Smad2 activation in cardiomyogenesis of embryonic stem cells. Circulation Research 101 78-87.
56. Kumar M, Jordan N, Melton D & Grapin-Botton A 2003 Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Developmental Biology 259 109-122.
57. Lamba P, Santos MM, Philips DP & Bernard DJ 2006 Acute regulation of murine follicle-stimulating hormone beta subunit transcription by activin A. Journal of Molecular Endocrinology 36 201-220.
58. Lamba P, Khivansara V, D'Alessio AC, SantosMM& Bernard DJ 2008 Paired-like homeodomain transcription factors 1 and 2 regulate follicle-stimulating hormone beta-subunit transcription through a conserved cis-element. Endocrinology 149 3095-3108.
59. Lara-Pezzi E, Felkin LE, Birks EJ, Sarathchandra P, Panse KD, George R, Hall JL, Yacoub MH, Rosenthal N & Barton PJR 2008 Expression offollistatin-related genes is altered in heart failure. Endocrinology 149 5822-5827.
60. Lee MJ, Yang CW, Jin DC, Chang YS, Bang BK & Kim YS 2003 Bone morphogenetic protein-7 inhibits constitutive and interleukin-1b-induced monocyte chemoattractant protein-1 expression in human mesangial cells: role for JNK/AP-1 pathway. Journal of Immunology 170 2557-2563.
61. Li L, Yi Z, Seno M & Kojima I 2004 Activin A and betacellulin: effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats. Diabetes 53 608-615.
62. Lin SY, Craythorn RG, O'Connor AE, Matzuk MM, Girling JE, Morrison JR & de Kretser DM 2008 Female infertility and disrupted angiogenesis are actions of specific follistatin isoforms. Molecular Endocrinology 22 415-429.
63. Mamin A & Philippe J 2006 Activin A decreases glucagon and arx gene expression in α cell lines. Molecular Endocrinology 21 259-273.
64. Martins da Silva SJ, Bayne RA, Cambray N, Hartley PS, McNeilly AS & Anderson RA 2004 Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation. Developmental Biology 266 334-345.
65. Mather JP, Attie KM, Woodruff TK, Rice GC & Phillips DM 1990 Activin stimulates spermatogonial proliferation in germ-Sertoli cell cocultures from immature rat testis. Endocrinology 127 3206-3214.
66. Mather JP, Woodruff TK & Krummen LA 1992 Paracrine regulation of reproductive function by inhibin and activin. Proceedings of the Society for Experimental Biology and Medicine 201 1-15.
67. Mather JP, Moore A & Li RH 1997 Activins, inhibins, and follistatins: further thoughts on a growing family of regulators. Proceedings of the Society for Experimental Biology and Medicine 215 209-222.
68. Mathews LS & Vale WW 1993 Molecular and functional characterization of activin receptors. Receptor 3 173-181.
69. Matzuk MM, Kumar TR & Bradley A 1995a Different phenotypes for mice deficient in either activins or activin receptor type II. Nature 374 356-360.
70. Matzuk MM, Kumar TR, Vassilli A, Bickenbach RR, Roop DR, Jaenisch R & Bradley A 1995b Functional analysis of activins during mammalian development. Nature 374 354-356.
71. Matzuk MM, Lu N, Vogel HJ, Sellheyer K, Roop DR & Bradley A 1995c Multiple defects and perinatal death in mice deficient in follistatin. Nature 374 360-363.
72. McGillivray SM, Thackray VG, Coss D & Mellon PL 2007 Activin and glucocorticoids synergistically activate follicle-stimulating hormone betasubunit gene expression in the immortalized LbetaT2 gonadotrope cell line. Endocrinology 148 762-773.
73. Menke DB & Page DC 2002 Sexually dimorphic gene expression in the developing mouse gonad. Gene Expression Patterns 2 359-367.
74. Mfopou JK & Bouwens L 2008 Hedgehog signals in pancreatic differentiation from embryonic stem cells: revisiting the neglected. Differentiation 76 107-117.
75. Mfopou JK, De GV, Xu X, Heimberg H & Bouwens L 2007 Sonic hedgehog and other soluble factors from differentiating embryoid bodies inhibit pancreas development. Stem Cells 25 1156-1165.
76. Michel U, Ebert S, Phillips D & NauR 2003a Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia. European Journal of Endocrinology 148 559-564.
77. Michel U, Gerber J, E O'Connor A, Bunkowski S, Bruck W, Nau R & Phillips DJ 2003b Increased activin levels in cerebrospinal fluid of rabbits with bacterial meningitis are associated with activation of microglia. Journal of Neurochemistry 86 238-245.
78. Mukherjee A, Sidis Y, Mahan A, Raher MJ, Xia Y, Rosen ED, Bloch KD, Thomas MK & Schneyer AL 2007 FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults. PNAS 104 1348-1353.
79. Myers M, Gay E, McNeilly AS, Fraser HM & Duncan WC 2007 In vitro evidence suggests activin-A may promote tissue remodeling associated with human luteolysis. Endocrinology 148 3730-3739.
80. Myers M, van den Driesche S, McNeilly AS & Duncan WC 2008 Activin A reduces luteinisation of human luteinised granulosa cells and has opposing effects to human chorionic gonadotropin in vitro. Journal of Endocrinology 199 201-212.
81. Nostro MC, Cheng X, Keller GM & Gadue P 2008 Wnt, activin, and BMP signaling regulate distinct stages in the developmental pathway from embryonic stem cells to blood. Cell Stem Cell 2 60-71.
82. Ogawa K, Abe K, Kurosawa N, Kurohmaru M, Sugino H, Takahashi M & Hayashi Y 1993 Expression of alpha, beta A and beta B subunits of inhibin or activin and follistatin in rat pancreatic islets. FEBS Letters 319 217-220.
83. Ogawa T, Yogo K, Ishida N & Takeya T 2003 Synergistic effects of activin and FSH on hyperphosphorylation of Rb and G1/S transition in rat primary granulosa cells. Molecular and Cellular Endocrinology 210 31-38.
84. Ogawa K, Funaba M, Chen Y & Tsujimoto M 2006 Activin A functions as a Th2 cytokine in the promotion of the alternative activation of macrophages. Journal of Immunology 177 6787-6794.
85. Ogawa K, Saito A, Matsui H, Suzuki H, Ohtsuka S, Shimosato D, Morishita Y, Watabe T, Niwa H & Miyazono K 2007 Activin-nodal signaling is involved in propagation of mouse embryonic stem cells. Journal of Cell Science 120 55-65.
86. Ogawa K, Funaba M & Tsujimoto M 2008 A dual role of activin A in regulating immunoglobulin production of B cells. Journal of Leukocyte Biology 83 1451-1458.
87. Okuma Y, Saito K, O'Connor AE, Phillips DJ, de Kretser DM & Hedger MP 2005 Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro. Journal of Endocrinology 185 99-110.
88. Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massague J & Niehrs C 1999 Silencing of TGF-beta signalling by the pseudoreceptor BAMBI. Nature 401 480-485.
89. Ota F, Maeshima A, Yamashita S, Ikeuchi H, Kaneko Y, Kuroiwa T, Hiromura K, Ueki K, Kojima I & Nojima Y 2003 Activin A induces cell proliferation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis and Rheumatism 48 2442-2449.
90. Pangas SA, Jorgez CJ, Tran M, Agno J, Li X, Brown CW, Kumar TR & Matzuk MM 2007 Intraovarian activins are required for female fertility. Molecular Endocrinology 21 2458-2471.
91. Park Y, Maizels ET, Feiger ZJ, Alam H, Peters CA, Woodruff TK, Unterman TG, Lee EJ, Jameson JL & Hunzicker-Dunn M 2005 Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad. Journal of Biological Chemistry 280 9135-9148.
92. Park MK, Han C, Lee KH, Hong SH, Kim HS, Lee YJ, Jeong IK, Noh JH, Yang TY, Lee MS et al. 2007 Effects of activin A on pancreatic ductal cells in streptozotocin-induced diabetic rats. Transplantation 83 925-930.
93. Pearson S, Sroczynska P, Lacaud G & Kouskoff V 2008 The stepwise specification of embryonic stem cells to hematopoietic fate is driven by sequential exposure to Bmp4, activin A, bFGF and VEGF. Development 135 1525-1535.
94. Phillips BW, Hentze H, Rust WL, Chen QP, Chipperfield H, Tan EK, Abraham S, Sadasivam A, Soong PL, Wang ST et al. 2007 Directed differentiation of human embryonic stem cells into the pancreatic endocrine lineage. Stem Cells and Development 16 561-578.
95. Riccioli A, Starace D, Galli R, Fuso A, Scarpa S, Palombi F, De Cesaris P, Ziparo E & Filippini A 2006 Sertoli cells initiate testicular innate immune responses through TLR activation. Journal of Immunology 177 7122-7130.
96. Robson NC, Phillips DJ, McAlpine T, Shin A, Svobodova S, Toy T, Pillay V, Kirkpatrick N, Zanker D, Wilson K et al. 2008 Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production. Blood 111 2733-2743.
97. Saito S, Sidis Y, Mukherjee A, Xia Y & Schneyer A 2005 Differential biosynthesis and intracellular transport of follistatin isoforms and follistatin-like-3. Endocrinology 146 5052-5062.
98. Schneyer AL, Rzucidlo DA, Sluss PM & Crowley WF Jr. 1994 Charactrerization of unique binding kinetics of follistatin and activin or inhbin in serum. Endocrinology 135 667-674.
99. Schneyer AL, Hall HA, Lambert-Messerlian G, Wang QF, Sluss P & Crowley WF Jr 1996 Follistatin-activin complexes in human serum and follicular fluid differ immunologically and biochemically. Endocrinology 137 240-247.
100. Schneyer A, Tortoriello D, Sidis Y, Keutmann H, Matsuzaki T & Holmes W 2001 Follistatin-related protein (FSRP): a new member of the follistatin gene family. Molecular and Cellular Endocrinology 180 33-38.
101. Schneyer AL, Wang Q, Sidis Y & Sluss PM 2004 Differential distribution of follistatin isoforms: application of a new FS315-specific immunoassay. Journal of Clinical Endocrinology and Metabolism 89 5067-5075.
102. Schneyer AL, Sidis Y, Gulati A, Sun JL, Keutmann H & Krasney PA 2008 Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. Endocrinology 149 4589-4595.
103. Shafiee-Kermani F, Han SO & Miller WL 2007 Chronic gonadotropin-releasing hormone inhibits activin induction of the ovine folliclestimulating hormone beta-subunit: involvement of 30,50-cyclic adenosine monophosphate response element binding protein and nitric oxide synthase type I. Endocrinology 148 3346-3355.
104. Sharpe RM, McKinnell C, Kivlin C & Fisher JS 2003 Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125 769-784.
105. Shi Y, Hou L, Tang F, Jiang W, Wang P, Ding M & Deng H 2005 Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid. Stem Cells 23 656-662.
106. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D et al. 1992 Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359 693-699.
107. Sidis Y, Schneyer AL, Sluss PM, Johnson LN & Keutmann HT 2001 Follistatin: essential role for the N-terminal domain in activin binding and neutralization. Journal of Biological Chemistry 276 17718-17726.
108. Sidis Y, Tortoriello DV, Holmes WE, Pan Y, Keutmann HT & Schneyer AL 2002 Follistatin-related protein and follistatin differentially neutralize endogenous vs. exogenous activin. Endocrinology 143 1613-1624.
109. Sidis Y, Schneyer AL & Keutmann HT 2005 Heparin and activin-binding determinants in follistatin and FSTL3. Endocrinology 146 130-136.
110. Sidis Y, Mukherjee A, Keutmann H, Delbaere A, Sadatsuki M & Schneyer A 2006 Biological activity of follistatin isoforms and follistatin like-3 are dependent on differential cell surface binding and specificity for activin, myostatin and BMP's. Endocrinology 147 3586-3597.
111. Smart NG, Apelqvist AA, Gu X, Harmon EB, Topper JN, MacDonald RJ & Kim SK 2006 Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. PLoS Biology 4 e39.
112. Smith C, Yndestad A, Halvorsen B, Ueland T, Waehre T, Otterdal K, Scholz H, Endresen K, Gullestad L, Froland SS et al. 2004 Potential antiinflammatory role of activin A in acute coronary syndromes. Journal of the American College of Cardiology 44 369-375.
113. Smith JR, Vallier L, Lupo G, Alexander M, Harris WA & Pedersen RA 2008 Inhibition of activin/nodal signaling promotes specification of human embryonic stem cells into neuroectoderm. Developmental Biology 313 107-117.
114. Spady TJ, Shayya R, Thackray VG, Ehrensberger L, Bailey JS & Mellon PL 2004 Androgen regulates follicle-stimulating hormone beta gene expression in an activin-dependent manner in immortalized gonadotropes. Molecular Endocrinology 18 925-940.
115. Stamler R, Keutmann HT, Sidis Y, Kattamuri C, Schneyer A & Thompson TB 2008 The structure of FSTL3.activin A complex: differential binding of n-terminal domains influences follistatin-type antagonist specificity. Journal of Biological Chemistry 283 32831-32838.
116. Sugino K, Kurosawa N, Nakamura T, Takio K, Shimasaki S, Ling N, Titani K & Sugino H 1993 Molecular heterogeneity of follistatin, an activin-binding protein. Journal of Biological Chemistry 68 15579-15587.
117. Sugino H, Sugino K, Hashimoto O, Shoji H & Nakamura T 1997 Follistatin and its role as an activin-binding protein. Journal of Medical Investigation 44 1-14.
118. Sumi T, Tsuneyoshi N, Nakatsuji N & Suemori H 2008 Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/beta-catenin, activin/nodal and BMP signaling. Development 135 2969-2979.
119. Suszko MI, Lo DJ, Suh H, Camper SA & Woodruff TK 2003 Regulation of the rat follicle-stimulating hormone β-subunit promoter by activin. Molecular Endocrinology 17 318-332.
120. Suszko MI, Balkin DM, Chen Y & Woodruff TK 2005 Smad3 mediates activin-induced transcription of follicle-stimulating hormone beta-subunit gene. Molecular Endocrinology 19 1849-1858.
121. Suszko MI, Antenos M, Balkin DM & Woodruff TK 2008 Smad3 and Pitx2 cooperate in stimulation of FSHbeta gene transcription. Molecular and Cellular Endocrinology 281 27-36.
122. Thackray VG & Mellon PL 2008 Synergistic induction of follicle-stimulating hormone beta-subunit gene expression by gonadal steroid hormone receptors and Smad proteins. Endocrinology 149 1091-1102.
123. Thompson TB, Woodruff TK & Jardetzky TS 2003 Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions. EMBO Journal 22 1555-1566.
124. Thompson TB, Lerch TF, Cook RW,Woodruff TK & Jardetzky TS 2005 The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding. Developmental Cell 9 535-543.
125. Tortoriello DV, Sidis Y, Holtzman DA, Holmes WE & Schneyer AL 2001 Human follistatin-related protein: a structural homologue of follistatin with nuclear localization. Endocrinology 142 3426-3434.
126. Totsuka Y, Tabuchi M, Kojima I, Shibai H & Ogata E 1988 A novel action of activin A: stimulation of insulin secretion in rat pancreatic islets. Biochemical and Biophysical Research Communications 156 335-339.
127. Tremblay KD, Hoodless PA, Bikoff EK & Robertson EJ 2000 Formation of the definitive endoderm in mouse is a Smad2-dependent process. Development 127 3079-3090.
128. Tsuchida K, Nakatani M, Yamakawa N, Hashimoto O, Hasegawa Y & Sugino H 2004 Activin isoforms signal through type I receptor serine/threonine kinase ALK7. Molecular and Cellular Endocrinology 220 59-65.
129. Tsuchida K, Nakatani M, Uezumi A, Murakami T & Cui X 2008 Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocrine Journal 55 11-21.
130. Vale W, Rivier C, Hsueh A, Campen C, Meunier H, Bicsak T, Vaughan J, Corrigan A, Bardin W, Sawchenko P et al. 1988 Chemical and biological characterization of the inhibin family of protein hormones. Recent Progress in Hormone Research 44 1-34.
131. Vallier L, Alexander M & Pedersen RA 2005 Activin/nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells. Journal of Cell Science 118 4495-4509.
132. Vassalli A, Matzuk MM, Gardner HA, Lee KF & Jaenisch R 1994 Activin/ inhibin beta B subunit gene disruption leads to defects in eyelid development and female reproduction. Genes and Development 8 414-427.
133. Verspohl EJ, Ammon HP & Wahl MA 1993 Activin A: its effects on rat pancreatic islets and the mechanism of action involved. Life Sciences 53 1069-1078.
134. Wada M, Shintani Y, Kosaka M, Sano T, Hizawa K & Saito S 1996 Immunohistochemical localization of activin A and follistatin in human tissues. Endocrine Journal 43 375-385.
135. Wang SY, Tai GX, Zhang PY, Mu DP, Zhang XJ & Liu ZH 2008a Inhibitory effect of activin A on activation of lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Cytokine 42 85-91.
136. Wang Y, Fortin J, Lamba P, Bonomi M, Persani L, Roberson MS & Bernard DJ 2008b Activator protein-1 and smad proteins synergistically regulate human follicle-stimulating hormone beta-promoter activity. Endocrinology 149 5577-5591.
137. Weiss J, Harris PE, Halvorson LM, Crowley WF & Jameson JL 1992 Dynamic regulation of follicle-stimulating hormone-beta messinger ribonucleic acid levels by activin and gonadotropin-releasing hormone in perifused rat pituitary cells. Endocrinology 131 1403-1408.
138. Welt C, Sidis Y, Keutmann H & Schneyer A 2002 Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium. Experimental Biology and Medicine 227 724-752.
139. Willems E & Leyns L 2008 Patterning of mouse embryonic stem cell-derived pan-mesoderm by activin A/nodal and Bmp4 signaling requires fibroblast growth factor activity. Differentiation 76 745-759.
140. Wilson KM, Smith AI & Phillips DJ 2006 Stimulatory effects of lipopolysaccharide on endothelial cell activin and follistatin. Molecular and Cellular Endocrinology 253 30-35.
141. Wu Z, Zhang W, Chen G, Cheng L, Liao J, Jia N, Gao Y, Dai H, Yuan J, Cheng L et al. 2008 Combinatorial signals of activin/nodal and bone morphogenic protein regulate the early lineage segregation of human embryonic stem cells. Journal of Biological Chemistry 283 24991-25002.
142. Xia Y, Sidis Y & Schneyer A 2004 Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice. Molecular Endocrinology 18 979-994.
143. Xia Y, O'Shea T, Almahbobi G & McFarlane JR 2008a Changes in ovarian follistatin levels during the oestrous cycle in sheep may serve as an intraovarian regulator. Reproduction in Domestic Animals (in press: DOI 10.1016/J.anireprosci.2008.08.022).
144. Xia Y, O'Shea T & McFarlane JR 2008b Changes in concentrations of follistatin in maternal plasma and foetal fluids during pregnancy and parturition in sheep. Animal Reproduction Science.
145. Xiao L, Yuan X & Sharkis SJ 2006 Activin A maintains self-renewal and regulates FGF, Wnt and BMP pathways in human embryonic stem cells. Stem Cells 28 1476-1480.
146. Xu RH, Sampsell-Barron TL, Gu F, Root S, Peck RM, Pan G, Yu J, Antosiewicz-Bourget J, Tian S, Stewart R et al. 2008 NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. Cell Stem Cell 3 196-206.
147. Yamaoka T, Idehara C, Yano M, Matsushita T, Yamada T, Ii S, Moritani M, Hata J, Sugino H, Noji S et al. 1998 Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. Journal of Clinical Investigation 102 294-301.
148. Yao HH, Matzuk MM, Jorgez CJ, Menke DB, Page DC, Swain A & Capel B 2004 Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis. Developmental Dynamics 230 210-215.
149. Yao HH-C, Aardema J & Holthusen K 2006a Sexually dimorphic regulation of inhibin beta B in establishing gonadal vasculature in mice. Biology of Reproduction 74 978-983.
150. Yao S, Chen S, Clark J, Hao E, Beattie GM, Hayek A & Ding S 2006b Longterm self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions. PNAS 103 6907-6912.
151. Zhang YQ, Zhang H, Maeshima A, Kurihara H, Miyagawa J, Takeuchi T & Kojima I 2002 Up-regulation of the expression of activins in the pancreatic duct by reduction of the beta-cell mass. Endocrinology 143 3540-3547.
152. Zhang XJ, Li Y, Tai GX, Xu GY, Zhang PY, Yang Y, Lao FX & Liu ZH 2005 Effects of activin A on the activities of the mouse peritoneal macrophages. Cellular & Molecular Immunology 2 63-67.
153. Zhang H, Bailey JS, Coss D, Lin B, Tsutsumi R, Lawson MA, Mellon PL & Webster NJG 2006 Activin modulates the transcriptional response of LssT2 cells to gonadotropin-releasing hormone and alters cellular