Activin A in Mammalian Physiology

Abstract

Activins are dimeric glycoproteins belonging to the transforming growth factor beta superfamily and resulting from the assembly of two beta subunits, which may also be combined with alpha subunits to form inhibins. Activins were discovered in 1986 following the isolation of inhibins from porcine follicular fluid, and were characterized as ovarian hormones that stimulate follicle stimulating hormone (FSH) release by the pituitary gland. In particular, activin A was shown to be the isoform of greater physiological importance in humans. The current understanding of activin A surpasses the reproductive system and allows its classification as a hormone, a growth factor, and a cytokine. In more than 30 yr of intense research, activin A was localized in female and male reproductive organs but also in other organs and systems as diverse as the brain, liver, lung, bone, and gut. Moreover, its roles include embryonic differentiation, trophoblast invasion of the uterine wall in early pregnancy, and fetal/neonate brain protection in hypoxic conditions. It is now recognized that activin A overexpression may be either cytostatic or mitogenic, depending on the cell type, with important implications for tumor biology. Activin A also regulates bone formation and regeneration, enhances joint inflammation in rheumatoid arthritis, and triggers pathogenic mechanisms in the respiratory system. In this 30-yr review, we analyze the evidence for physiological roles of activin A and the potential use of activin agonists and antagonists as therapeutic agents.

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

“…A number of intraand extracellular inhibitors, including follistatin and follistatin-related proteins that bind and disable activin-A, coordinate its effects. [31][32][33][34][35] One well established effects of activin-A is it´s role in the wound cure and fracture consolidation. Deregulation of this process is related to pathological collagen accumulation.…”

Endocrine-Disrupting Chemicals in Human Fetal Growth

“…Among the various hormones involved (thyroid hormones, insulin, Growth hormone (GH) variants, leptin, cortisol) a key role is played by Insulin-like growth Factor (IGF)-1 and IGF-2 [2], and it is important to cite (see the following chapters) that the inflammatory and the IGF systems also interact [3]. In recent years, additional factors were discovered and proved to be of upmost importance [4][5][6] such as Activin, A.; Human corionic gonadotropin (HCG), and retinoic acid and its receptors in animal models [7].…”

The rhythm of healthy kidneys

“…Activin A is a glycoprotein that either alone or after forming heterodimers together with activin B acts as an endocrine factor. Initially, recognized as a positive regulator for folliclestimulating hormone (FSH) release, it has become clear that particularly activin A plays many more roles in normal physiology and disease processes (for review see reference [1]). Activin A belongs to the superfamily of transforming growth factor β (TGF-β) and is signaling through ActRIIA/B receptors and Smads to alter transcription of target genes.…”