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Gene Review

FST  -  follistatin

Homo sapiens

Synonyms: Activin-binding protein, FS, Follistatin
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Disease relevance of FST


Psychiatry related information on FST

  • AIMS: To define clinically relevant cut-off points for severe fear of self-injecting (FSI) and self-testing (FST) (phobia) in insulin-treated patients with diabetes, and to estimate the magnitude of these phobias in our research population [7].
  • Individuals with high dental fear had a statistically significantly higher number of decayed surfaces (DS), decayed teeth, (DT) and missing teeth (MT) but a statistically significantly lower number of filled surfaces (FS), filled teeth (FT), functional surfaces (FSS), and functional teeth (FST) [8].
  • Exogenous administration of FS and related muramyl peptides results in an increase in slow-wave sleep (SWS) [9].

High impact information on FST

  • In the process other factors such as activin and follistatin were serendipitously discovered [10].
  • Ruiz i Altaba describes a possible model for anteroposterior patterning involving ;lanar signals for amphibian, avian and mammalian embryos, compares the axial patterning of the neural plate with the patterning of insect epithelia, and discussed possible roles of noggin, follistatin and hedgehog-related genes in neural induction and patterning [11].
  • Follistatin was first described in 1987 as a follicle-stimulating hormone inhibiting substance present in ovarian follicular fluid [12].
  • In this review we focus on the biochemical characteristics of follistatin and its interaction with activin and discuss the emerging role of these proteins as potent tissue regulators in the gonad, pituitary gland, pregnancy membranes, vasculature, and liver [12].
  • Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines) [13].

Chemical compound and disease context of FST


Biological context of FST


Anatomical context of FST


Associations of FST with chemical compounds

  • Tumor necrosis factor alpha and interferon-gamma significantly stimulated follistatin expression but down-regulated expression of gremlin [20].
  • Mutation of any of these to Asp or Ala either reduced or eliminated FS bioactivity and disrupted distant epitopes for heparin binding (FS domain 1) or antibody recognition (FS domain 2), suggesting their role in maintaining the conformational integrity of the domain and possibly the FS molecule as a whole [22].
  • The cDNA of this new evolutionarily conserved gene (named FLRG for Follistatin-Related Gene) codes for a secreted glycoprotein of the follistatin-module-protein family [25].
  • The addition of anti-FS antibody to cultures with BMP-2 and Dex augmented bone nodule formation [21].
  • The activin-FS complex in hFF elutes at approximately 200-300 kDa, is immunoprecipitated by anti-hFS288 monoclonal antibodies, and binds to sulfate Cellufine matrix, all characteristics similar to those of recombinant human FS288 [26].
  • Our results reveal a key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling and provide new evidence for a regulatory interaction between HH and activin/BMP signaling in hair follicle development and BCC [27].

Physical interactions of FST

  • Introduction of the full domain from FS conferred heparin binding to FSTL3, but activin binding was abolished [28].
  • A continuous sequence comprising the N-terminal domain and followed by FS domains 1 and 2 fulfills the minimum structural requirement for activin binding and FS bioactivity [22].
  • We provide data which show that Follistatin binds BMP-7 and BMP-2 at low affinities and that the binding is reversible [29].

Regulatory relationships of FST

  • Activin A stimulated total ir-FS production by undifferentiated and partially differentiated GC, but inhibited total ir-FS production by fully differentiated GC [24].
  • Follistatin regulates bone morphogenetic protein-7 (BMP-7) activity to stimulate embryonic muscle growth [29].
  • Interestingly, the effect of EGF/TGFalpha could be blocked by cotreatment with follistatin, a potent binding protein for activin, an ovarian growth factor belonging to the TGFbeta superfamily [30].
  • Thus, the FST-deficient rat gonadotrope cell is a model that allows for the investigation of factors regulating FSHbeta expression, which might otherwise involve the autocrine/paracrine actions of FST [31].
  • Activin A and follistatin influence expression of somatostatin in the ciliary ganglion in vivo [32].

Other interactions of FST


Analytical, diagnostic and therapeutic context of FST


  1. Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma. Welt, C.K., Lambert-Messerlian, G., Zheng, W., Crowley, W.F., Schneyer, A.L. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  2. Deregulation of the activin/follistatin system in hepatocarcinogenesis. Grusch, M., Drucker, C., Peter-V??r??smarty, B., Erlach, N., Lackner, A., Losert, A., Macheiner, D., Schneider, W.J., Hermann, M., Groome, N.P., Parzefall, W., Berger, W., Grasl-Kraupp, B., Schulte-Hermann, R. J. Hepatol. (2006) [Pubmed]
  3. Inhibin, activin, follistatin, activin receptors and beta-glycan gene expression in the placental tissue of patients with pre-eclampsia. Casagrandi, D., Bearfield, C., Geary, J., Redman, C.W., Muttukrishna, S. Mol. Hum. Reprod. (2003) [Pubmed]
  4. Inhibin subunits, follistatin and activin receptors in the human teratocarcinoma cell line Tera-2. de Jong, F.H., de Winter, J.P., Wesseling, J.G., Timmerman, M.A., van Genesen, S., van den Eijnden-van Raaij, A.J., van Zoelen, E.J. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  5. Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma. Ciarmela, P., Florio, P., Sigurdardottir, M., Toti, P., Maguer-Satta, V., Rimokh, R., Altomare, A., Tosi, P., Petraglia, F. Eur. J. Endocrinol. (2004) [Pubmed]
  6. Follistatin suppresses the production of experimental multiple-organ metastasis by small cell lung cancer cells in natural killer cell-depleted SCID mice. Ogino, H., Yano, S., Kakiuchi, S., Muguruma, H., Ikuta, K., Hanibuchi, M., Uehara, H., Tsuchida, K., Sugino, H., Sone, S. Clin. Cancer Res. (2008) [Pubmed]
  7. Phobia of self-injecting and self-testing in insulin-treated diabetes patients: opportunities for screening. Mollema, E.D., Snoek, F.J., Heine, R.J., van der Ploeg, H.M. Diabet. Med. (2001) [Pubmed]
  8. Are there differences in oral health and oral health behavior between individuals with high and low dental fear? Schuller, A.A., Willumsen, T., Holst, D. Community dentistry and oral epidemiology. (2003) [Pubmed]
  9. Are antibiotic effects on sleep behavior in the rat due to modulation of gut bacteria? Brown, R., Price, R.J., King, M.G., Husband, A.J. Physiol. Behav. (1990) [Pubmed]
  10. Nonsteroidal signals originating in the gonads. Ackland, J.F., Schwartz, N.B., Mayo, K.E., Dodson, R.E. Physiol. Rev. (1992) [Pubmed]
  11. Pattern formation in the vertebrate neural plate. Ruiz i Altaba, A. Trends Neurosci. (1994) [Pubmed]
  12. Follistatin: a multifunctional regulatory protein. Phillips, D.J., de Kretser, D.M. Frontiers in neuroendocrinology. (1998) [Pubmed]
  13. Visual motion processing investigated using contrast agent-enhanced fMRI in awake behaving monkeys. Vanduffel, W., Fize, D., Mandeville, J.B., Nelissen, K., Van Hecke, P., Rosen, B.R., Tootell, R.B., Orban, G.A. Neuron (2001) [Pubmed]
  14. Melanoma cells secrete follistatin, an antagonist of activin-mediated growth inhibition. Stove, C., Vanrobaeys, F., Devreese, B., Van Beeumen, J., Mareel, M., Bracke, M. Oncogene (2004) [Pubmed]
  15. Activin inhibits basal and androgen-stimulated proliferation and induces apoptosis in the human prostatic cancer cell line, LNCaP. Wang, Q.F., Tilly, K.I., Tilly, J.L., Preffer, F., Schneyer, A.L., Crowley, W.F., Sluss, P.M. Endocrinology (1996) [Pubmed]
  16. Expression of FLRG, a novel activin A ligand, is regulated by TGF-beta and during hematopoiesis [corrected]. Maguer-Satta, V., Bartholin, L., Jeanpierre, S., Gadoux, M., Bertrand, S., Martel, S., Magaud, J.P., Rimokh, R. Exp. Hematol. (2001) [Pubmed]
  17. Attenuation of bleomycin-induced pulmonary fibrosis by follistatin. Aoki, F., Kurabayashi, M., Hasegawa, Y., Kojima, I. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  18. Physiological and regulatory roles of activin A in late pregnancy. Jenkin, G., Ward, J., Loose, J., Schneider-Kolsky, M., Young, R., Canny, B., O'Connor, A., de Kretser, D., Wallace, E. Mol. Cell. Endocrinol. (2001) [Pubmed]
  19. Biological activity of follistatin isoforms and follistatin-like-3 is dependent on differential cell surface binding and specificity for activin, myostatin, and bone morphogenetic proteins. Sidis, Y., Mukherjee, A., Keutmann, H., Delbaere, A., Sadatsuki, M., Schneyer, A. Endocrinology (2006) [Pubmed]
  20. Differential gene expression and regulation of the bone morphogenetic protein antagonists follistatin and gremlin in normal and osteoarthritic human chondrocytes and synovial fibroblasts. Tardif, G., Hum, D., Pelletier, J.P., Boileau, C., Ranger, P., Martel-Pelletier, J. Arthritis Rheum. (2004) [Pubmed]
  21. Follistatin restricts bone morphogenetic protein (BMP)-2 action on the differentiation of osteoblasts in fetal rat mandibular cells. Abe, Y., Abe, T., Aida, Y., Hara, Y., Maeda, K. J. Bone Miner. Res. (2004) [Pubmed]
  22. The role of follistatin domains in follistatin biological action. Keutmann, H.T., Schneyer, A.L., Sidis, Y. Mol. Endocrinol. (2004) [Pubmed]
  23. FLRG, an activin-binding protein, is a new target of TGFbeta transcription activation through Smad proteins. Bartholin, L., Maguer-Satta, V., Hayette, S., Martel, S., Gadoux, M., Bertrand, S., Corbo, L., Lamadon, C., Morera, A.M., Magaud, J.P., Rimokh, R. Oncogene (2001) [Pubmed]
  24. Regulation of follistatin production by rat granulosa cells in vitro. Shintani, Y., Dyson, M., Drummond, A.E., Findlay, J.K. Endocrinology (1997) [Pubmed]
  25. FLRG (follistatin-related gene), a new target of chromosomal rearrangement in malignant blood disorders. Hayette, S., Gadoux, M., Martel, S., Bertrand, S., Tigaud, I., Magaud, J.P., Rimokh, R. Oncogene (1998) [Pubmed]
  26. Follistatin-activin complexes in human serum and follicular fluid differ immunologically and biochemically. Schneyer, A.L., Hall, H.A., Lambert-Messerlian, G., Wang, Q.F., Sluss, P., Crowley, W.F. Endocrinology (1996) [Pubmed]
  27. GLI2-specific transcriptional activation of the bone morphogenetic protein/activin antagonist follistatin in human epidermal cells. Eichberger, T., Kaser, A., Pixner, C., Schmid, C., Klingler, S., Winklmayr, M., Hauser-Kronberger, C., Aberger, F., Frischauf, A.M. J. Biol. Chem. (2008) [Pubmed]
  28. Heparin and activin-binding determinants in follistatin and FSTL3. Sidis, Y., Schneyer, A.L., Keutmann, H.T. Endocrinology (2005) [Pubmed]
  29. Follistatin regulates bone morphogenetic protein-7 (BMP-7) activity to stimulate embryonic muscle growth. Amthor, H., Christ, B., Rashid-Doubell, F., Kemp, C.F., Lang, E., Patel, K. Dev. Biol. (2002) [Pubmed]
  30. Epidermal growth factor and TGFalpha promote zebrafish oocyte maturation in vitro: potential role of the ovarian activin regulatory system. Pang, Y., Ge, W. Endocrinology (2002) [Pubmed]
  31. Stimulation of FSHbeta transcription by blockade of endogenous pituitary follistatin production: Efficacy of adenoviral-delivered antisense RNA in the rat. Haisenleder, D.J., Aylor, K.W., Burger, L.L., Dalkin, A.C., Marshall, J.C. Endocrine (2006) [Pubmed]
  32. Activin A and follistatin influence expression of somatostatin in the ciliary ganglion in vivo. Darland, D.C., Nishi, R. Dev. Biol. (1998) [Pubmed]
  33. Differential effect of activin A and BMP-7 on myofibroblast differentiation and the role of the Smad signaling pathway. You, L., Kruse, F.E. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  34. Expression of activin and inhibin subunits, receptors and binding proteins in Human adrenocortical neoplasms. Hofland, J., Timmerman, M.A., de Herder, W.W., van Schaik, R.H., de Krijger, R.R., de Jong, F.H. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  35. Regulatory expression of bone morphogenetic protein-6 system in aldosterone production by human adrenocortical cells. Inagaki, K., Otsuka, F., Suzuki, J., Otani, H., Takeda, M., Kano, Y., Miyoshi, T., Yamashita, M., Ogura, T., Makino, H. Regul. Pept. (2007) [Pubmed]
  36. Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured sympathetic neurons. Beck, H.N., Drahushuk, K., Jacoby, D.B., Higgins, D., Lein, P.J. BMC neuroscience [electronic resource]. (2001) [Pubmed]
  37. Follistatin production by skin fibroblasts and its regulation by dexamethasone. Kawakami, S., Fujii, Y., Winters, S.J. Mol. Cell. Endocrinol. (2001) [Pubmed]
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