Table 1.
Biological functions of activins and inhibins
| Proteins | Tissue/cell types | Biological functions | References |
|---|---|---|---|
| Development | |||
| Activin | Human embryonic stem cells | Maintenance of pluripotency | Wu et al. 2008; Xu et al. 2008 |
| Activin A | Craniofacial (mouse) | Whisker, palate, and tooth development | Matzuk et al. 1995d; Brown et al. 2000 |
| Activin A | Mouse tissues | Supports total body weight gain and the growth of gonads, fat, and liver | Brown et al. 2000; Li et al. 2009 |
| Activin B | Mammary gland | Stroma-supported ductal elongation, alveolar morphogenesis, and luminal expansion | Vassalli et al. 1994; Robinson and Hennighausen 1997 |
| Activin B | Craniofacial (mouse) | Prenatal eyelid fusion | Schrewe et al. 1994; Vassalli et al. 1994 |
| Activin D | All stages, Xenopus embryos | Mesoderm induction | Oda et al. 1995 |
| Nervous system | |||
| Activin A | E18 rat retinal progenitors | Induces differentiation into rod photoreceptors | Davis et al. 2000 |
| Activin A | Cultured P19 teratoma cells, rat B50 nerve cells and chick neural retinal cells | Increased survival beyond life span under normal culture conditions | Schubert et al. 1990 |
| Activin A | Rat mesencephalon dopaminergic cells | Protects against N-methyl-4-phenylpiridinium ion toxicity | Krieglstein et al. 1995 |
| Activin A | Hippocampus and dorsolateral striatum | Protection against neuronal death induced by hypoxic-ischemic brain injury | Wu et al. 1999 |
| Activin A | Striatal cholinergic interneurons | Protects against chemically induced neurodegeneration | Hughes et al. 1999 |
| Activin B + TGF-β1 | Oligodendrocytes | Together enhance proliferation, viability, maturation, and myelination during embryonic development | Dutta et al. 2014 |
| Activin orthologs | Drosophila embryos | Promote neuron growth and photoreceptor axon targeting | Zhu et al. 2008 |
| Reproduction | |||
| Activin | Pituitary gonadotropes | Augments GnRH-induced FSH release | Ling et al. 1986a; Vale et al. 1986 |
| Activin A | Cultured ovarian granulosa cells | Increases DNA synthesis, augmented by FSH; increases expression of estrogen receptor; enhances proliferation of cells from human pre-ovulatory follicles | Kipp et al. 2007 |
| Activin A | Cultured ovarian theca cells | Blocks LH-induced androgen production | Hillier et al. 1991b |
| Activin A | Cultured ovarian luteal cells | Blocks LH-induced progesterone production | Di Simone et al. 1994 |
| Activin B | Developing gonad | Coelomic vessel formation in developing male gonads | Yao et al. 2006 |
| Activin A | Fetal Sertoli cells | Activin A from fetal Leydig cells supports Sertoli cell proliferation and testis cord elongation | Archambeault and Yao 2010 |
| Activin A | Cultured Sertoli cells | Enhances proliferation alone or in combination with FSH; induces production of inhibin and follistatin; causes reversion to an immature, proliferative state | Buzzard et al. 2003; Nicholls et al. 2012 |
| Activin A | Cultured Leydig cells | Blocks LH-induced androgen production | Mauduit et al. 1991 |
| Activin A | Germ/Sertoli cell coculture | Increases germ cell/Sertoli cell ratio | Meehan et al. 2000 |
| Inhibin | Ovarian granulosa cells | Antagonizes proliferation of granulosa cells at the single-layer follicle stage; ovarian tumor suppression | Matzuk et al. 1992; Wu et al. 2004 |
| Inhibin | Ovarian theca cells | Promotes steroidogenesis | Wu et al. 2004 |
| Inhibin B | Testis | Possible paracrine role in spermatogenesis by supporting germ, Sertoli, and Leydig cell interactions | Clifton et al. 2002; Kumanov et al. 2006 |
| Inhibin | Pituitary gonadotropes | Negative regulator of FSH production and release | Setchell and Jacks 1974; De Jong and Sharpe 1976 |
| Inhibin | Ovarian granulosa cells | Antagonizes proliferation of granulosa cells at the single-layer follicle stage | Wu et al. 2004 |
| Inhibin | Ovarian theca cells | Promotes steroidogenesis | Wu et al. 2004 |
| Inhibin | Placenta | Blocks activin-mediated steroidogenesis and HCG production | Petraglia et al. 1989; Jones et al. 2006 |
| Body composition and energy metabolism | |||
| Activin A | Liver | Induces hepatocyte apoptosis | Schwall et al. 1993 |
| Activin A | Human preadipocytes, mouse 3T3-L1 preadipocytes | Increases proliferation while inhibiting differentiation | Zaragosi et al. 2010 |
| Activin B | 3T3-L1 mature adipocytes | Reduces lipolysis and lipase gene expression | Magnusson et al. 2010 |
| Activin A + HGF | AR42J-B13 pancreatic progenitor cells | Relaxation of neurogenin-3 transcriptional repression, enhancing differentiation | Ogihara et al. 2003 |
| ActRIIB signaling | Adipose and muscle | Influences lean/fat body mass ratio, “britening” of white adipose, peripheral glucose uptake and hepatic glucose production | Akpan et al. 2009; Fournier et al. 2012; Koncarevic et al. 2012; Zhang et al. 2012 |
| Activins A and B | Pancreatic islets | Affect islet cell differentiation, growth, calcium signaling, α-/β-cell ratio, and insulin release | Yamaoka et al. 1998; Bertolino et al. 2008; Bonomi et al. 2012 |
| Activin ortholog (dawdle) | Drosophila embryos | Regulates triglyceride, glycogen, and glucose metabolism and corresponding Krebs cycle, oxphos, and fatty acid oxidation enzymes | Ghosh and O’Connor 2014 |
| Activin C | Liver | Possible effects on hepatocellular proliferation | Chabicovsky et al. 2003; Takamura et al. 2005; Wada et al. 2005 |
| Inflammation | |||
| Activin A | Mouse macrophage RAW264.7 | Increases IL-1β, IL-6, CD80, macrophage activation, and phagocytosis | Ge et al. 2009 |
| Activin A | Human peripheral blood monocytes | Supports the proinflammatory M2 macrophage phenotype | Sierra-Filardi et al. 2011 |
| Activin B | Human hepatoma and mouse primary hepatocytes | Increases expression of hepcidin during inflammation, mediated by Smad1/5/8 phosphorylation | Besson-Fournier et al. 2012 |
| Erythropoiesis | |||
| Activin A | K562 erythroleukemia cells | Augments EPO-dependent hemoglobin production | Yu et al. 1987 |
| Inhibin | K562 human leukemia and primary human bone marrow cells | Suppresses activin-induced differentiation and EPO-induced CFU formation | Yu et al. 1987 |
| Activin | Human bone marrow–derived erythrocyte precursors | Enhanced proliferation | Yu et al. 1987 |
| Miscellaneous | |||
| Activins A, B, and AB | Myoblasts | Inhibits myotube differentiation | Souza et al. 2008 |
| Activin A | Muscle | Negatively regulates muscle mass | Chen et al. 2015 |
| Activin | Human breast cancer T47D cells | p38 MAPK-mediated growth inhibition | Cocolakis et al. 2001 |
| Activins A and B | Human neuroblastoma and rat pheochromocytoma | Protect against serum withdrawal-induced apoptosis | Kupershmidt et al. 2007 |
| Inhibin | Bone | Positive effects on bone mineral density | Vural et al. 2005; Perrien et al. 2006; Perrien et al. 2007 |
| Activin | Keratinocytes | Stress fiber formation and enhanced cell migration through non-Smad-mediated signaling | Zhang et al. 2005 |
| Inhibin | Adrenal cortex | Tumor suppression | Matzuk et al. 1992; Looyenga and Hammer 2006 |