activins

Activins are dimeric secreted proteins belonging to the transforming growth factor beta (TGF-β) superfamily. They are formed from two beta subunits, which in humans are encoded by INHBA (beta-A), INHBB (beta-B), INHBC (beta-C), and INHBE (beta-E). The mature forms most studied are activin A (beta-A/beta-A), activin B (beta-B/beta-B), and activin AB (beta-A/beta-B); additional beta subunits can assemble into other activin dimers such as activin C or activin E.

Activins signal by binding to type II receptors (ACVR2A or ACVR2B) and recruiting type I receptors (such as ACVR1B/ALK-4 or ALK-7). This triggers phosphorylation of receptor-regulated SMADs (SMAD2 and SMAD3), which form a complex with SMAD4 and regulate transcription in the nucleus. The signaling pathway can be modulated by extracellular antagonists such as follistatin, a high-affinity binder that neutralizes activins, and by inhibins, which act as antagonists of activin signaling in concert with the co-receptor betaglycan.

Physiological roles of activins are diverse. They regulate reproductive function by influencing follicle-stimulating hormone (FSH) synthesis and secretion, and they affect gonadal development and function. Beyond reproduction, activins participate in embryonic development, organogenesis, cell proliferation and differentiation, wound healing, immune responses, and metabolic processes. Their activity is context-dependent and tightly controlled by binding proteins and receptor expression.

Clinical relevance includes associations with reproductive disorders, fibrosis, and cancer. Because of their regulatory roles, activin signaling pathways are investigated as potential therapeutic targets for fertility treatment, tissue regeneration, and tumor biology.