ANTI-ACTIVIN-A ANTIBODY (IGY) SPECIFICALLY NEUTRALIZES VARIOUS ACTIVIN-A ACTIVITIES

Activin A (beta(A) beta(A)), originally isolated from ovarian follicul ar fluids as a follicule-stimulating hormone (FSH) secretion stimulato r, has also been identified as an erythroid differentiation factor (ED F), a neuron survival factor and a mesoderm-inducing factor, Thus, act ivin A is a multifunctional factor, and further studies on its physiol ogical function are important. However, It is very difficult to produc e a specific antibody to neutralize the activity of activin A because of its highly conserved amino acid sequence across mammalian species. In this study, we succeeded in generating an antibody against activin A, which can neutralize several activities of activin A, such as the s timulation of FSH secretion from pituitary cells and the induction of the differentiation of erythrocytes In vitro. This antibody did not af fect the activity of activin B (beta(B) beta(B)), which Induces the di fferentiation of erythrocytes in vitro, and the activity of inhibin A (alpha beta(A)), which inhibits FSH secretion from pituitary in vitro, but slightly neutralized that of activin AB (beta(A) beta(B)) Western blotting analysis showed that this antibody recognized both dimeric a nd monomeric forms of the beta(A) subunit of activin and inhibin, Thes e results suggest that this antibody recognizes the beta(A) subunit of activin and specifically neutralizes the activity of a dimer of the b eta(A) subunit, activin A, Furthermore, by the addition of this antibo dy to the culture medium, the development of murine embryos was suppre ssed, suggesting that endogenous activin A plays an important role in murine development, These results indicate the usefulness of this anti body for studies of endogenous activin actions.