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Transforming Growth Factor β: A Multifunctional Regulatory Peptide with Actions in the Reproductive System

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Growth Factors in Reproduction

Part of the book series: Serono Symposia, USA ((SERONOSYMP))

Abstract

Transforming growth factor β (TGFβ) was first identified as a factor that could induce normal rat kidney (NRK) fibroblasts to form colonies in soft agar in the presence of epidermal growth factor (EGF) (1). Even though TGFβ has the ability to act in this classical assay for transformation, we now know that it is also a mediator of normal cellular physiology and has especially important actions in the processes of embryonic development, tissue remodeling, and wound healing (2). Almost all cells in culture synthesize TGFβ and have TGFβ receptors (3), and immunoreactive TGFβ has been found in a number of embryonic and adult murine tissues (4–5). These data suggest that TGFβ has widespread biological actions. In this chapter we review the chemistry and biology of the TGFβ family, with special emphasis on some of the biological actions of TGFβ that are most likely to be important in the function of the reproductive tract. A brief overview of the actions of TGFβ on gonadal cell types is given here; more details can be found in other chapters of this volume.

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References

  1. Roberts AB, Anzano MA, Lamb LC, Smith JM, Sporn MB. New class of transforming growth factor potentiated by epidermal growth factor. Proc Natl Acad Sci USA 1981; 78:5339–5343.

    Article  PubMed  CAS  Google Scholar 

  2. Roberts AB, Sporn MB. The transforming growth factor-betas. In: Sporn MB, Roberts AB, eds. Handbook of experimental pharmacology. Heidelberg: Springer-Verlag, 1990; 95:419–472.

    Google Scholar 

  3. Wakefield LM, Smith DM, Masui T, Harris CC, Sporn MB. Distribution and modulation of the cellular receptors for transforming growth factor-beta. J Cell Biol 1987; 105:965–975.

    Article  PubMed  CAS  Google Scholar 

  4. Heine UI, Flanders KC, Roberts AB, Munoz EF, Sporn MB. Role of transforming growth factor-β in the development of the mouse embryo. J Cell Biol 1987; 105:2861–2876.

    Article  PubMed  CAS  Google Scholar 

  5. Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB, Sporn MB. Cell type specific expression of transforming growth factor-beta 1 in adult and neonatal mouse tissue. J Cell Biol 1989; 108:661–669.

    Article  PubMed  CAS  Google Scholar 

  6. Derynck R, Jarrett JA, Chen EY, et al. Human transforming growth factor-beta cDNA sequence and expression in tumor cell lines. Nature 1985; 316:4377–4379.

    Article  Google Scholar 

  7. Madisen L, Webb NR, Rose TM, et al. Transforming growth factor-β2: cDNA cloning and sequence analysis. DNA 1988; 7:1–8.

    Article  PubMed  CAS  Google Scholar 

  8. de Martin R, Haendler B, Hofer-Warbinek R, et al. Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-β gene family. EMBO J 1987; 6:3673–3677.

    PubMed  Google Scholar 

  9. Jakowlew SB, Dillard PJ, Sporn MB, Roberts AB. Complementary deoxyribonucleic acid cloning of mRNA encoding transforming growth factor-β2 from chicken embryo chondrocytes. Growth Factors (in press).

    Google Scholar 

  10. Dijke P, Hanson P, Iwata KK, Pieler C, Foulkes JG. Identification of a new member of the transforming growth factor-β gene family. Proc Natl Acad Sci USA 1988; 85: 4715–4719.

    Article  PubMed  Google Scholar 

  11. Derynck R, Lindquist PB, Lee A, et al. A new type of transforming growth factor-β, TGF-β3. EMBO J 1988; 7:3737–3743.

    PubMed  CAS  Google Scholar 

  12. Denhez F, Lafyatis R, Kondaiah P, Roberts AB, Sporn MB. Cloning by polymerase chain reaction of a new mouse TGF-β, mTGF-β3. Growth Factors (in press).

    Google Scholar 

  13. Jakowlew SB, Dillard PJ, Kondaiah P, Sporn MB, Roberts AB. Complementary deoxyribonucleic acid cloning of a novel transforming growth factor-β messenger ribonucleic acid from chick embryo chondrocytes. Mol Endocrinol 198; 2:747–755.

    Google Scholar 

  14. Jakowlew SB, Dillard PJ, Sporn MB, Roberts AB. Complementary deoxyribonucleic acid cloning of an mRNA encoding transforming growth factor-beta 4 from chicken embryo chondrocytes. Mol Endocrinol 1988; 2:1186–1195.

    Article  PubMed  CAS  Google Scholar 

  15. Kondaiah P, Sands MJ, Smith JM, et al. Identification of a novel transforming growth factor β (TGF-β5) mRNA in Xenopus laevis. J Biol Chem 1990; 265:1089–1093.

    PubMed  CAS  Google Scholar 

  16. Roberts AB, Kondaiah P, Rosa F, et al. Mesoderm induction in Xenopus laevis distinguishes between the various TGF-β isoforms. Growth Factors (submitted).

    Google Scholar 

  17. Roberts AB, Rosa F, Roche NS, et al. Isolation and characterization of TGF-β2 and TGF-β5 from medium conditioned by Xenopus XTC cells. Growth Factors (in press).

    Google Scholar 

  18. Jennings JC, Mohan S, Iinkhart TA, Widstrom R, Baylink DJ. Comparison of the biological activities of TGF-β1 and TGF-β2: Differential activity in endothelial cells. J Cell Physiol 1988; 137:167–172.

    Article  PubMed  CAS  Google Scholar 

  19. Glick AB, Flanders KC, Danielpour D, Yuspa SH, Sporn MB. Retinoic acid induces transforming growth factor-β2 in cultured keratinocytes and mouse epidermis. Cell Regulation 1989; 1:87–97.

    PubMed  CAS  Google Scholar 

  20. Mason AJ, Hayflick JS, Ling N, et al. Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-β. Nature 1985; 318:659–663.

    Article  PubMed  CAS  Google Scholar 

  21. Ling N, Ying SY, Ueno N, et al. Pituitary FSH is released by a heterodimer of the β-subunits from the two forms of inhibin. Nature 1986; 321:779–782.

    Article  PubMed  CAS  Google Scholar 

  22. Cate RL, Mattaliano RJ, Hession C, et al. Isolation of the bovine and human genes for mullerian inhibiting substance and expression of the human gene in animal cells. Cell 1986; 45:685–698.

    Article  PubMed  CAS  Google Scholar 

  23. Padgett RW, St. Johnston RD, Gelbart WM. A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-beta family. Nature 1987; 325:81–84.

    Article  PubMed  CAS  Google Scholar 

  24. Weeks DL, Melton DA. A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-β. Cell 1987; 51:861–867.

    Article  PubMed  CAS  Google Scholar 

  25. Lyons K, Graycar JL, Lee A, et al. Vgr-1, a mammalian gene related to Xenopus Vg-1, is a member of the transforming growth factor β gene superfamily. Proc Natl Acad Sci USA 1989; 86:4554–4558.

    Article  PubMed  CAS  Google Scholar 

  26. Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: Molecular clones and activities. Science 1988; 242:1528–1534.

    Article  PubMed  CAS  Google Scholar 

  27. Kimelman D, Kirschner M. Synergistic induction of mesoderm by FGF and TGF-β and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell 1987; 51:869–877.

    Article  PubMed  CAS  Google Scholar 

  28. Rappolee DA, Brenner CA, Schultz R, Mark D, Werb Z. Developmental expression of PDGF, TGF-a, and TGF-β genes in preimplantation mouse embryos. Science 1988; 242:1823–1825.

    Article  Google Scholar 

  29. Lehnert SA, Akhurst RJ. Embryonic expression pattern of TGF-beta type 1 RNA suggests both paracrine and autocrine mechanisms of action. Development 1988; 104:263–273.

    PubMed  CAS  Google Scholar 

  30. Robey PG, Young MF, Flanders, KC, et al. Osteoblasts synthesize and respond to TGF-beta in vitro. J Cell Biol 1987; 105:457–463.

    Article  PubMed  CAS  Google Scholar 

  31. Seyedin SM, Thomas TC, Thompson AY, Rosen DM, Piez KA. Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci USA 1985:82:2267–2271.

    Article  PubMed  CAS  Google Scholar 

  32. Sporn MB, Roberts AB. Peptide growth factors are multifunctional. Nature 1988; 332:217–219.

    Article  PubMed  CAS  Google Scholar 

  33. Wakefield LM, Smith DL, Flanders KC, Sporn MB. Latent transforming growth factor-β from human platelets. J Biol Chem 1988; 263:7646–7654.

    PubMed  CAS  Google Scholar 

  34. Rosen DM, Stempien SA, Thompson AY, Seyedin PR. Transforming growth factor-beta modulates the expression of osteoblast and chondroblast phenotypes in vitro. J Cell Physiol 1988; 134:337–346.

    Article  PubMed  CAS  Google Scholar 

  35. Silberstein GB, Daniel CW. Reversible inhibition of mammary gland growth by transforming growth factor-β. Science 1987; 237:291–293.

    Article  PubMed  CAS  Google Scholar 

  36. Gabrielson EW, Gerwin BI, Harris CC, Roberts AB, Sporn MB, Lechner JF. Stimulation of DNA synthesis in cultured primary human mesothelial cells by specific growth factor. FASEB J 1988; 2:2717–2721.

    PubMed  CAS  Google Scholar 

  37. Takahashi T, Nelson K, Goods L, McLachlan JA. Transforming growth factor-β promotes the growth of mouse uterus and vagina, in vivo [Abstract]. J Cell Biochem 1989; 13B:201.

    Google Scholar 

  38. Madri JA, Pratt BM, Tucker A. Phenotypic modulation of endothelial cells by transforming growth factor-β depends upon the composition and organization of the extracellular matrix. J Cell Biol 1988; 106:1375–1384.

    Article  PubMed  CAS  Google Scholar 

  39. Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med 1987; 165:251–256.

    Article  PubMed  CAS  Google Scholar 

  40. Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into extracellular matrix. J Biol Chem 1986; 261:4337–4345.

    PubMed  CAS  Google Scholar 

  41. Rossi P, Karsenty G, Roberts AB, Roche NS, Sporn MB, de Crombrugghe B. A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-β. Cell 1988; 52:405–414.

    Article  PubMed  CAS  Google Scholar 

  42. Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH. Transforming growth factor-β increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest 1987; 79:1285–1288.

    Article  PubMed  CAS  Google Scholar 

  43. Roberts CJ, Birkenmeier TM, McQuillan JJ, et al. Transforming growth factor-β stimulates the expression of fibronectin and of both subunits of the human fibronectin receptor by cultured human lung fibroblasts. J Biol Chem 1988; 263:4586–4592.

    PubMed  CAS  Google Scholar 

  44. Junqueira LC, Carneiro J, Long JA, eds. Basic histology. Norwalk, CT: Appleton-Century-Crofts, 1986.

    Google Scholar 

  45. Kehrl JH, Roberts AB, Wakefield LM, Jakowlew SB, Sporn MB, Fauci AS. Transforming growth factor beta is an important immunomodulatory protein for human B-lymphocytes. J Immunol 1986; 137:3855–3860.

    PubMed  CAS  Google Scholar 

  46. Kehrl JH, Wakefield LM, Roberts AB, et al. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med 1986; 163:1037–1050.

    Article  PubMed  CAS  Google Scholar 

  47. Tamada H, McMaster MT, Flanders KC, Andrews GK, Dey SK. Cell type-specific expression of TGF-β in the mouse uterus during the periimplantation period. Mol Endocrinol (submitted).

    Google Scholar 

  48. Flanders KC, Cissel DS, Mullen LT, Danielpour D, Sporn MB, Roberts AB. Antibodies to transforming growth factor-β2 peptides: Specific detection of TGF-β in immunoassays. Growth Factors (in press).

    Google Scholar 

  49. Clark DA, Flanders KC, Banwatt D, et al. Suppressor cells in murine pregnancy decidua produce an immunosuppressive molecule related to transforming growth factor β-2. J Immunol (in press).

    Google Scholar 

  50. Ying S-Y, Becker A, Baird A, et al. Type beta transforming growth factor (TGF-β) is a potent stimulator of the basal secretion of follicle stimulating hormone (FSH) in a pituitary monolayer system. Biochem Biophys Res Commun 1986; 135:950–956.

    Article  PubMed  CAS  Google Scholar 

  51. Benahmed M, Cochet C, Kermidas M, Chauvin MA, Morera AM. Evidence for a FSH dependent secretion of a receptor reactive transforming growth factor-β-like material by immature Sertoli cells in primary culture. Biochem Biophys Res Commun 1988; 154:1222–1231.

    Article  PubMed  CAS  Google Scholar 

  52. Skinner MK, Moses HL. Transforming growth factor-β gene expression and action in the seminiferous tubule: Peritubular cell-Sertoli cell interactions. Mol Endocrinol 1989; 3:625–634.

    Article  PubMed  CAS  Google Scholar 

  53. Morera AM, Cochet C, Keramidas M, Chauvin MA, de Peretti E, Benahmed M. Direct regulating effects of transforming growth factor β on the Leydig cell steroidogenesis in primary culture. J Steroid Biochem 1988; 30:443–447.

    Article  PubMed  CAS  Google Scholar 

  54. Avallet O, Vigier M, Perrard-Sapori MH, Saez JM. Transforming growth factor β inhibits Leydig cell functions. Biochem Biophys Res Commun 1987; 146:575–581.

    Article  PubMed  CAS  Google Scholar 

  55. Lin T, Blaisdell J, Haskell JF. Transforming growth factor-β inhibits Leydig cell steroidogenesis in primary culture. Biochem Biophys Res Commun 1987; 146:387–394.

    Article  PubMed  CAS  Google Scholar 

  56. Adashi EY, Resnick CE, Hernandez ER, May JV, Purchio AF, Twardzik DR. Ovarian transforming growth factor-β (TGF-β): Cellular site(s) and mechanism(s) of action. Mol Cell Endocrinol 1989; 61:247–256.

    Article  PubMed  CAS  Google Scholar 

  57. Ying S-Y, Becker A, Ling N, Ueno N, Guillemin R. Inhibin and beta type transforming growth factor (TGF-β) have opposite modulating effects on the follicle stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells. Biochem Biophys Res Commun 1986; 136:969–975.

    Article  PubMed  CAS  Google Scholar 

  58. Feng P, Catt KJ, Knecht M. Transforming growth factor β regulates the inhibitory actions of epidermal growth factor during granulosa cell differentiation. J Biol Chem 1986; 261:14167–14170.

    PubMed  CAS  Google Scholar 

  59. Dorrington J, Chuma AV, Bendell JJ. Transforming growth factor β and follicle-stimulating hormone promote rat granulosa cell proliferation. Endocrinology 1988; 123:353–359.

    Article  PubMed  CAS  Google Scholar 

  60. Skinner MK, Keski-Oja J, Osteen KG, Moses HL. Ovarian thecal cells produce transforming growth factor-β which can regulate granulosa cell growth. Endocrinology 1987; 121:786–792.

    Article  PubMed  CAS  Google Scholar 

  61. Knecht M, Feng P, Catt K. Bifunctional role of transforming growth factor-β during granulosa cell development. Endocrinology 1987; 120:1243–1249.

    Article  PubMed  CAS  Google Scholar 

  62. Dodson WC, Schomberg DW. The effect of transforming growth factor-β on follicle-stimulating hormone induced differentiation of cultured rat granulosa cells. Endocrinology 1987; 120:512–516.

    Article  PubMed  CAS  Google Scholar 

  63. Kim I-C, Schomberg DW. The production of transforming growth factor-β activity by rat granulosa cell cultures. Endocrinology 1989; 124:1345–1351.

    Article  PubMed  CAS  Google Scholar 

  64. Ruegsegger Veit C, Assoian RK. Identification of transforming growth factor-beta in human ovarian follicular fluid [Abstract]. Endocrinology 1988; 122 (suppl):1227.

    Google Scholar 

  65. Magoffin DA, Gancedo B, Erickson GF. Transforming growth factor-β promotes differentiation of ovarian thecal-interstitial cells but inhibits androgen production. Endocrinology 1989; 125:1951–1958.

    Article  PubMed  CAS  Google Scholar 

  66. Ikeda T, Lioubin MN, Marquardt H. Human transforming growth factor type β2; production by a prostatic adenocarcinoma cell Une, purification, and initial characterization. Biochemistry 1987; 26:4337–4345.

    Article  Google Scholar 

  67. Komm BS, Terpening CM, Benz DJ, et al. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science 1988; 241:81–84.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. National Cancer Institute, Laboratory of Chemoprevention, Bethesda, Maryland, USA

    Kathleen C. Flanders, Belinda A. Marascalco, Anita B. Roberts & Michael B. Sporn

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  1. Kathleen C. Flanders
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  2. Belinda A. Marascalco
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  3. Anita B. Roberts
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  4. Michael B. Sporn
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Editors and Affiliations

  1. Duke University Medical Center, Durham, NC, 27710, USA

    David W. Schomberg PhD

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© 1991 Springer-Verlag New York, Inc.

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Flanders, K.C., Marascalco, B.A., Roberts, A.B., Sporn, M.B. (1991). Transforming Growth Factor β: A Multifunctional Regulatory Peptide with Actions in the Reproductive System. In: Schomberg, D.W. (eds) Growth Factors in Reproduction. Serono Symposia, USA. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3162-2_2

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  • DOI: https://doi.org/10.1007/978-1-4612-3162-2_2

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7819-1

  • Online ISBN: 978-1-4612-3162-2

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