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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.<\/jats:p>","DOI":"10.1152\/physrev.00002.2018","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T10:03:15Z","timestamp":1544608995000},"page":"739-780","source":"Crossref","is-referenced-by-count":184,"title":["Activin A in Mammalian Physiology"],"prefix":"10.1152","volume":"99","author":[{"given":"Enrrico","family":"Bloise","sequence":"first","affiliation":[{"name":"Department of Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica delle Marche, Ancona, Italy; Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Department of Molecular and Developmental Medicine, Obstetrics and Gynecological Clinic, University of Siena, Siena, Italy; and 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