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Gene Review

Inhba  -  inhibin beta-A

Mus musculus

Synonyms: Activin beta-A chain, Inhibin beta A chain, activin
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Disease relevance of Inhba


High impact information on Inhba

  • To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK) [6].
  • Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele [6].
  • The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin [7].
  • Secretion of activin by interstitial cells in the testis [8].
  • It is likely that, in the testis, the Leydig cells secrete activin and the Sertoli cells produce inhibin, or a combination of both [8].

Biological context of Inhba

  • Thus, the enlarged islets and beta cell number likely result from increased activin action [9].
  • Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line [10].
  • Although both activin and glucocorticoids are notable regulators of FSHbeta by themselves, we find that cotreatment results in a synergistic interaction on the mouse FSHbeta promoter at the level of the gonadotrope using transient transfection of a reporter gene into the LbetaT2 immortalized gonadotrope-derived cell line [10].
  • In vitro, the biological effects of activin A are neutralized by the soluble binding protein follistatin [1].
  • The kinetics and distribution of activin A and follistatin protein were assessed in lung tissue and bronchoalveolar lavage fluid and measured in relation to airway eosinophilia, goblet cell metaplasia and Th2 cytokine production in mediastinal lymph nodes [1].

Anatomical context of Inhba

  • Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells [11].
  • These cell lines include mesodermal (MES-1), neuroepithelial (EPI-7), and visceral endoderm-like (END-2) cell types, expressing both inhibin beta A and beta B subunit mRNAs [12].
  • By contrast, two species (6 and 3 kb) of activin receptor ActRII mRNA were identified in equal intensity in all four Leydig tumor cell lines [13].
  • Identification of tocopherol-associated protein as an activin/TGF-beta-inducible gene in mast cells [3].
  • Activin may also play a positive role in oocyte maturation and acquisition of developmental competence [14].

Associations of Inhba with chemical compounds

  • Concomitantly, activin, TGF-beta and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles [14].
  • TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors [15].
  • Hippocampal neurons from dnActRIB mice were significantly more vulnerable to intracerebroventricular injection of the excitotoxin kainic acid than those from control littermates, indicating a crucial role of endogenous activin in the rescue of neurons from excitotoxic insult [16].
  • Xlmx1b was found to be upregulated by activin A and RA inhibited this upregulation in a concentration dependant manner [17].
  • Second, SB203580 inhibited the inhibitory effect of activin A on the colony-forming activity of K562 cells using the methylcellulose colony assay, indicating that activin A inhibits K562 colony formation by activating p38 MAPK [18].

Physical interactions of Inhba


Regulatory relationships of Inhba


Other interactions of Inhba


Analytical, diagnostic and therapeutic context of Inhba


  1. Follistatin is a candidate endogenous negative regulator of activin A in experimental allergic asthma. Hardy, C.L., O'Connor, A.E., Yao, J., Sebire, K., de Kretser, D.M., Rolland, J.M., Anderson, G.P., Phillips, D.J., O'Hehir, R.E. Clin. Exp. Allergy (2006) [Pubmed]
  2. Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs. van Schaik, R.H., Wierikx, C.D., Looijenga, L.H., Oosterhuis, J.W., de Jong, F.H. Br. J. Cancer (1997) [Pubmed]
  3. Identification of tocopherol-associated protein as an activin/TGF-beta-inducible gene in mast cells. Funaba, M., Murakami, M., Ikeda, T., Ogawa, K., Tsuchida, K., Sugino, H. Biochim. Biophys. Acta (2006) [Pubmed]
  4. Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells. Bianco, C., Adkins, H.B., Wechselberger, C., Seno, M., Normanno, N., De Luca, A., Sun, Y., Khan, N., Kenney, N., Ebert, A., Williams, K.P., Sanicola, M., Salomon, D.S. Mol. Cell. Biol. (2002) [Pubmed]
  5. Autoimmune targeted disruption of the pituitary-ovarian axis causes premature ovarian failure. Altuntas, C.Z., Johnson, J.M., Tuohy, V.K. J. Immunol. (2006) [Pubmed]
  6. Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Brown, C.W., Houston-Hawkins, D.E., Woodruff, T.K., Matzuk, M.M. Nat. Genet. (2000) [Pubmed]
  7. Pitx2 determines left-right asymmetry of internal organs in vertebrates. Ryan, A.K., Blumberg, B., Rodriguez-Esteban, C., Yonei-Tamura, S., Tamura, K., Tsukui, T., de la Peña, J., Sabbagh, W., Greenwald, J., Choe, S., Norris, D.P., Robertson, E.J., Evans, R.M., Rosenfeld, M.G., Izpisúa Belmonte, J.C. Nature (1998) [Pubmed]
  8. Secretion of activin by interstitial cells in the testis. Lee, W., Mason, A.J., Schwall, R., Szonyi, E., Mather, J.P. Science (1989) [Pubmed]
  9. FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults. Mukherjee, A., Sidis, Y., Mahan, A., Raher, M.J., Xia, Y., Rosen, E.D., Bloch, K.D., Thomas, M.K., Schneyer, A.L. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  10. Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line. McGillivray, S.M., Thackray, V.G., Coss, D., Mellon, P.L. Endocrinology (2007) [Pubmed]
  11. Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells. Ogawa, K., Saito, A., Matsui, H., Suzuki, H., Ohtsuka, S., Shimosato, D., Morishita, Y., Watabe, T., Niwa, H., Miyazono, K. J. Cell. Sci. (2007) [Pubmed]
  12. Modulation of activin expression by type beta transforming growth factors. van der Kruijssen, C.M., Feijen, A., Huylebroeck, D., van den Eijnden-van Raaij, A.J. Exp. Cell Res. (1993) [Pubmed]
  13. Inhibin/activin subunits and activin receptor are co-expressed in Leydig tumor cells. Chen, C.L., Pignataro, O.P., Feng, Z.M. Mol. Cell. Endocrinol. (1993) [Pubmed]
  14. TGF-beta superfamily members and ovarian follicle development. Knight, P.G., Glister, C. Reproduction (2006) [Pubmed]
  15. Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. ten Dijke, P., Yamashita, H., Sampath, T.K., Reddi, A.H., Estevez, M., Riddle, D.L., Ichijo, H., Heldin, C.H., Miyazono, K. J. Biol. Chem. (1994) [Pubmed]
  16. Transgenic Mice Expressing Dominant-negative Activin Receptor IB in Forebrain Neurons Reveal Novel Functions of Activin at Glutamatergic Synapses. Müller, M.R., Zheng, F., Werner, S., Alzheimer, C. J. Biol. Chem. (2006) [Pubmed]
  17. Isolation and growth factor inducibility of the Xenopus laevis Lmx1b gene. Haldin, C.E., Nijjar, S., Massé, K., Barnett, M.W., Jones, E.A. Int. J. Dev. Biol. (2003) [Pubmed]
  18. Activin A induces erythroid gene expressions and inhibits mitogenic cytokine-mediated K562 colony formation by activating p38 MAPK. Huang, H.M., Chiou, H.Y., Chang, J.L. J. Cell. Biochem. (2006) [Pubmed]
  19. The activin-binding protein follistatin is expressed in developing murine molar and induces odontoblast-like cell differentiation in vitro. Heikinheimo, K., Bègue-Kirn, C., Ritvos, O., Tuuri, T., Ruch, J.V. J. Dent. Res. (1997) [Pubmed]
  20. A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements. Howell, M., Inman, G.J., Hill, C.S. Development (2002) [Pubmed]
  21. Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Laurikkala, J., Pispa, J., Jung, H.S., Nieminen, P., Mikkola, M., Wang, X., Saarialho-Kere, U., Galceran, J., Grosschedl, R., Thesleff, I. Development (2002) [Pubmed]
  22. Compound disruption of smad2 accelerates malignant progression of intestinal tumors in apc knockout mice. Hamamoto, T., Beppu, H., Okada, H., Kawabata, M., Kitamura, T., Miyazono, K., Kato, M. Cancer Res. (2002) [Pubmed]
  23. Activin A stimulates type IV collagenase (matrix metalloproteinase-2) production in mouse peritoneal macrophages. Ogawa, K., Funaba, M., Mathews, L.S., Mizutani, T. J. Immunol. (2000) [Pubmed]
  24. Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair. Munz, B., Smola, H., Engelhardt, F., Bleuel, K., Brauchle, M., Lein, I., Evans, L.W., Huylebroeck, D., Balling, R., Werner, S. EMBO J. (1999) [Pubmed]
  25. The promotion of plasmacytoma tumor growth by mesenchymal stroma is antagonized by basic fibroblast growth factor induced activin A. Shoham, T., Sternberg, D., Brosh, N., Krupsky, M., Barda-Saad, M., Zipori, D. Leukemia (2001) [Pubmed]
  26. Activin regulates estrogen receptor gene expression in the mouse ovary. Kipp, J.L., Kilen, S.M., Woodruff, T.K., Mayo, K.E. J. Biol. Chem. (2007) [Pubmed]
  27. Developmental expression of activin/inhibin beta A, beta B, and alpha subunits, and activin receptor-IIB genes in preimplantation mouse embryos. Lu, R.Z., Matsuyama, S., Nishihara, M., Takahashi, M. Biol. Reprod. (1993) [Pubmed]
  28. Interaction between soluble type I receptor for bone morphogenetic protein and bone morphogenetic protein-4. Natsume, T., Tomita, S., Iemura, S., Kinto, N., Yamaguchi, A., Ueno, N. J. Biol. Chem. (1997) [Pubmed]
  29. Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents. Rohwedel, J., Maltsev, V., Bober, E., Arnold, H.H., Hescheler, J., Wobus, A.M. Dev. Biol. (1994) [Pubmed]
  30. Inhibins differentially antagonize activin and bone morphogenetic protein action in a mouse adrenocortical cell line. Farnworth, P.G., Stanton, P.G., Wang, Y., Escalona, R., Findlay, J.K., Ooi, G.T. Endocrinology (2006) [Pubmed]
  31. Basic fibroblast growth factor induces notochord formation and the expression of As-T, a Brachyury homolog, during ascidian embryogenesis. Nakatani, Y., Yasuo, H., Satoh, N., Nishida, H. Development (1996) [Pubmed]
  32. Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-alpha and p53-deficient mice: the role of activin as an autocrine growth factor. Shikone, T., Matzuk, M.M., Perlas, E., Finegold, M.J., Lewis, K.A., Vale, W., Bradley, A., Hsueh, A.J. Mol. Endocrinol. (1994) [Pubmed]
  33. Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. Murata, M., Eto, Y., Shibai, H., Sakai, M., Muramatsu, M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
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