We present the first evidence that activin action can be inhibited by IGF binding proteins. Our data show that nanomolar concentrations of IGFBP-4 and -5 can totally inhibit the activin-dependent increase in Inh-a expression. The finding that IGF-I reversed the inhibition suggests that the mechanism of the IGFBP could involve a reduction in bio-available IGF in the culture medium by forming an inactive complex of IGF and IGFBP. This possibility is supported by the evidence that anti-IGF-I antibody mimics the inhibitory effects of IGFBP-4 and -5 on Inh-a production. buy asthma inhaler
Because there is compelling evidence that rat GC produce IGF-I, it seems likely that the mechanism of IGFBP-4 and -5 inhibition of activin action is through a decrease in the concentration of GC-derived bioavailable IGF-I. Implicit in this notion is the new idea that the constitutive expression of IGF-I is mandatory for activin-de-pendent Inh-a expression. Our results raise the question of whether IGF-I may have a role in mediating other activin-dependent responses in the ovary or the effects of activin in other basic body tissues. In this regard, it is noteworthy that endogenous IGF-I is also required for activin-induced FSH receptor in rat GC (unpublished results).