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Gene Review

Inhbb  -  inhibin beta-B

Mus musculus

Synonyms: Activin beta-B chain, Inhibin beta B chain, activin
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Disease relevance of Inhbb

  • However, inham1/inham1, MT-FS+ mice exhibit a less severe wasting syndrome, lower serum activin levels, and a statistically significant prolonged survival in a number of cases compared with mice deficient in inhibin alone [1].
  • Although differentiation of murine erythroleukemia F5-5.fl cells is induced by activin, it is not induced by TGF-beta, suggesting that at some point TGF-beta signaling is defective [2].
  • They lack whiskers and lower incisors and have defects in their secondary palates, including cleft palate, demonstrating that activin-beta A must have a role during craniofacial development [3].
  • The present study demonstrates for the first time the abundant expression of activin A in murine lung tissues after BLM administration, suggesting that activin A may play a role in the pathogenesis of BLM-induced pulmonary fibrosis [4].
  • Our data indicate that the development of substances influencing activin expression or receptor binding should offer new ways to fight neuronal loss in ischemic and traumatic brain injury [5].

High impact information on Inhbb

  • 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].
  • Moreover, manipulation of the sidedness of either activin protein or Shh expression alters heart situs [7].
  • We show that expression of Xbra occurs as a result of mesoderm induction in Xenopus, both in response to the natural signal and in response to the mesoderm-inducing factors activin A and basic FGF [8].
  • Induction of activin A is essential for the neuroprotective action of basic fibroblast growth factor in vivo [5].
  • Mice lacking both activin subunits show the defects of both individual mutants but no additional defects, indicating that there is no functional redundancy between these proteins during embryogenesis [3].

Chemical compound and disease context of Inhbb


Biological context of Inhbb

  • Our results suggest that activin betaC and betaE are not essential for either embryonic development or liver function [12].
  • In contrast to the structurally related activin betaA and betaB subunits, which are necessary for embryonic development and pituitary follicle-stimulating hormone homeostasis, mice deficient in activin betaC and betaE were viable, survived to adulthood, and demonstrated no reproductive abnormalities [12].
  • During the period of organogenesis the sites of expression of activin receptors type IIA and IIB messenger RNA (mRNA) generally coincide with or are adjacent to the sites of beta subunit expression [13].
  • To provide evidence for biological significance of activin A stimulation of GnRHR gene expression, the response of a human gonadotropin alpha-subunit promoter/luciferase reporter gene (alpha Gon-Luc) to GnRH was assessed in alpha T3-1 cells pretreated with activin A [14].
  • To investigate further the effect of activin A on the transcription of the GnRHR gene, alpha T3-1 cells were transiently transfected with a mouse GnRHR promoter/luciferase reporter gene (GnRHR-Luc) and challenged with activin A [14].

Anatomical context of Inhbb

  • 5. Gene targeting in embryonic stem cells was used to generate mice with null mutations in either the individual activin betaC and betaE genes or both genes [12].
  • Little is known, however, about mesoderm formation in the mammalian embryo, and as one approach to investigating this we have studied activin and follistatin expression during early mouse development [15].
  • This demonstrates that ductal elongation and epithelial cell differentiation during puberty and pregnancy require activin/inhibin signalling from the stroma [16].
  • From 6.5- to 9.5-days post coitum (p.c.) activin beta A and beta B subunit expression was restricted to the decidua, while activin receptor type IIB messages were exclusively detected in the embryo [13].
  • Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expression of follistatin in primitive streak, somites and hindbrain [15].

Associations of Inhbb with chemical compounds

  • Activin A rapidly and transiently increased Smad7 messenger RNA (mRNA) levels of rat anterior pituitary (RAP), clonal gonadotrope (alpha T 3-1 and L beta T2), and corticotrope (AtT20) cells with an EC(50) of 0.1-0.2 nM [17].
  • Cycloheximide treatment inhibits induction of activin betaA, indicating a requirement for new protein synthesis [18].
  • 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 [19].
  • Preantral follicles (100-120 microm in diameter) harvested from adult mice and cultured in in vitro follicle culture system showed a significant increase in size and estrogen and inhibin secretion in response to FSH, but the administration of activin A blocked the effect of FSH [20].
  • Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs [4].

Physical interactions of Inhbb


Regulatory relationships of Inhbb

  • On the other hand, in the ovary, inhibin beta B is repressed by WNT4 and its downstream target follistatin, leading to the absence of the coelomic vessel [22].
  • By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells [23].
  • 8-Bromo-cAMP inhibited expression of inhibin alpha-subunit mRNA but stimulated expression of activin/inhibin beta A- and beta B-subunit mRNAs in placenta and decidua by the 3rd day of culture [24].
  • Smad7 selectively interferes with different pathways of activin signaling and inhibits erythroid leukemia cell differentiation [25].
  • Furthermore, although Madr2 remains unlocalized in ectodermal explants, addition of activin enhances the concentration of Madr2 in the nucleus [26].

Other interactions of Inhbb

  • Furthermore, TGF beta increased the amount of bioactive activin secreted by MES-1 and END-2 cells [27].
  • Follistatin is a modulator of gonadal tumor progression and the activin-induced wasting syndrome in inhibin-deficient mice [1].
  • Activin has a positive growth effect on gonadal tumor cells in culture and directly causes the cancer cachexia-like syndrome in inhibin-deficient mice via interaction with activin receptor type IIA in livers and stomachs [1].
  • Addition of cAMP derivative to MA-10 cells at 0.1 mM for 17 h or 1 mM for 5 h produced a two-fold increase in inhibin alpha-subunit mRNA levels, and small or no significant change in inhibin beta-B-subunit and ActRII mRNAs [28].
  • Here, we show by RNase protection that activin betaC transcripts are present in the liver beginning at embryonic day 11.5 (E11.5) whereas activin betaE expression is detected starting from E17 [12].

Analytical, diagnostic and therapeutic context of Inhbb

  • Using in situ hybridization we have studied the localization of the messenger RNAs encoding the inhibin/activin subunits (alpha, beta A, beta B), the activin-binding protein follistatin and activin receptors (IIA, IIB) in mouse embryos during postimplantation development [13].
  • Bioassays in which activin betaA expression is blocked or activin betaA is absent from the media indicate that activin betaA promotes the formation of mesenchymal cells in the endothelial cushions, which are required for normal septation [29].
  • The presence of activin betaA was demonstrated by Western blot analysis of the cardiocyte conditioned media (CCM) [29].
  • Using differential display PCR we have identified activin betaA as a gene associated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induced differentiation of a mouse limb bud cell line, MLB13MYC clone 17, from a prechondroblastic to an osteoblastic phenotype [18].
  • RNA synthesis of TGF-beta and activin A was measured by RT-PCR [30].


  1. Follistatin is a modulator of gonadal tumor progression and the activin-induced wasting syndrome in inhibin-deficient mice. Cipriano, S.C., Chen, L., Kumar, T.R., Matzuk, M.M. Endocrinology (2000) [Pubmed]
  2. mRNA expression of type I and type II receptors for activin, transforming growth factor-beta, and bone morphogenetic protein in the murine erythroleukemic cell line, F5-5.fl. Machida, H., Ogawa, K., Funaba, M., Mizutani, T., Tsujimoto, M. Eur. J. Endocrinol. (2000) [Pubmed]
  3. Functional analysis of activins during mammalian development. Matzuk, M.M., Kumar, T.R., Vassalli, A., Bickenbach, J.R., Roop, D.R., Jaenisch, R., Bradley, A. Nature (1995) [Pubmed]
  4. Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment. Matsuse, T., Fukuchi, Y., Eto, Y., Matsui, H., Hosoi, T., Oka, T., Ohga, E., Nagase, T., Orimo, H. Am. J. Respir. Cell Mol. Biol. (1995) [Pubmed]
  5. Induction of activin A is essential for the neuroprotective action of basic fibroblast growth factor in vivo. Tretter, Y.P., Hertel, M., Munz, B., ten Bruggencate, G., Werner, S., Alzheimer, C. Nat. Med. (2000) [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. A molecular pathway determining left-right asymmetry in chick embryogenesis. Levin, M., Johnson, R.L., Stern, C.D., Kuehn, M., Tabin, C. Cell (1995) [Pubmed]
  8. Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction. Smith, J.C., Price, B.M., Green, J.B., Weigel, D., Herrmann, B.G. Cell (1991) [Pubmed]
  9. Activin A and all-trans-retinoic acid cooperatively enhanced the functional activity of L-type Ca2+ channels in the neuroblastoma C1300 cell line. Fukuhara, S., Mukai, H., Munekata, E. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  10. Inhibition by 1alpha,25-dihydroxyvitamin D3 of activin A-induced differentiation of murine erythroleukemic F5-5 cells. Nagasaki, T., Hino, M., Inaba, M., Nishizawa, Y., Morii, H., Otani, S. Arch. Biochem. Biophys. (1997) [Pubmed]
  11. Activin synergistically increased c-jun mRNA in P19 embryonal carcinoma cells in the presence of retinoic acid. Momoi, T., Kawai, Y., Momoi, M., Etoh, Y. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  12. Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration. Lau, A.L., Kumar, T.R., Nishimori, K., Bonadio, J., Matzuk, M.M. Mol. Cell. Biol. (2000) [Pubmed]
  13. Expression of activin subunits, activin receptors and follistatin in postimplantation mouse embryos suggests specific developmental functions for different activins. Feijen, A., Goumans, M.J., van den Eijnden-van Raaij, A.J. Development (1994) [Pubmed]
  14. Transcriptional activation of the gonadotropin-releasing hormone receptor gene by activin A. Fernández-Vázquez, G., Kaiser, U.B., Albarracin, C.T., Chin, W.W. Mol. Endocrinol. (1996) [Pubmed]
  15. Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expression of follistatin in primitive streak, somites and hindbrain. Albano, R.M., Arkell, R., Beddington, R.S., Smith, J.C. Development (1994) [Pubmed]
  16. Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Robinson, G.W., Hennighausen, L. Development (1997) [Pubmed]
  17. Regulation and actions of Smad7 in the modulation of activin, inhibin, and transforming growth factor-beta signaling in anterior pituitary cells. Bilezikjian, L.M., Corrigan, A.Z., Blount, A.L., Chen, Y., Vale, W.W. Endocrinology (2001) [Pubmed]
  18. BMP-2 induces the expression of activin betaA and follistatin in vitro. Kearns, A.E., Demay, M.B. J. Cell. Biochem. (2000) [Pubmed]
  19. 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]
  20. Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage. Mizunuma, H., Liu, X., Andoh, K., Abe, Y., Kobayashi, J., Yamada, K., Yokota, H., Ibuki, Y., Hasegawa, Y. Endocrinology (1999) [Pubmed]
  21. The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse. Gu, Z., Nomura, M., Simpson, B.B., Lei, H., Feijen, A., van den Eijnden-van Raaij, J., Donahoe, P.K., Li, E. Genes Dev. (1998) [Pubmed]
  22. Sexually dimorphic regulation of inhibin Beta B in establishing gonadal vasculature in mice. Yao, H.H., Aardema, J., Holthusen, K. Biol. Reprod. (2006) [Pubmed]
  23. Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection. Maldonado, T.S., Kadison, A.S., Crisera, C.A., Grau, J.B., Alkasab, S.L., Longaker, M.T., Gittes, G.K. J. Gastrointest. Surg. (2000) [Pubmed]
  24. Cyclic AMP regulates expression of activin and inhibin subunit mRNAs in the mouse placenta and decidua: a short communication. Yamaguchi, M., Fujii, M., Miyake, A. Eur. J. Endocrinol. (1996) [Pubmed]
  25. Smad7 selectively interferes with different pathways of activin signaling and inhibits erythroid leukemia cell differentiation. Kitamura, K., Aota, S., Sakamoto, R., Yoshikawa, S.I., Okazaki, K. Blood (2000) [Pubmed]
  26. A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Baker, J.C., Harland, R.M. Genes Dev. (1996) [Pubmed]
  27. 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]
  28. 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]
  29. Expression and function of activin beta A during mouse cardiac cushion tissue formation. Moore, C.S., Mjaatvedt, C.H., Gearhart, J.D. Dev. Dyn. (1998) [Pubmed]
  30. Portal vein ligation and partial hepatectomy differentially influence growth of intrahepatic metastasis and liver regeneration in mice. Heinrich, S., Jochum, W., Graf, R., Clavien, P.A. J. Hepatol. (2006) [Pubmed]
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