Activin-lnduced Inhibin: DISCUSSION(3)

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Our results also provide evidence that tyrosine phosphorylation is important in determining the effects of activin on Inh-a production. This follows from the observation that the PTK inhibitor tyrphostin A23 totally eliminates activin-induced increases in Inh-a mRNA and protein production. Tyrphostins are a family of synthetic PTK inhibitors that have been reported to block autophosphorylation of both epidermal growth factor and IGF-I receptors. The absence of cytotoxic effects of A23 in our experiments confirm other studies with rat GC and studies with other cultured cell types showing that A23 is cytotoxic at concentrations > 120 |xM. Our results not only suggest that the activin-dependent changes in Inh-a require tyrosine phosphorylation (perhaps at the level of the type I IGF receptor), but they also provide important additional evidence to support our hypothesis that IGF-I signaling is obligatory for activin-regulated Inh-a gene expression.

In summary, we have presented evidence that endogenously produced IGF-I plays an essential role in the mechanisms underlying activin stimulation of Inh-a gene expression in rat GC. The functional significance of this relationship between IGF-I and activin action remains to be densitometry after normalization for cyclophilin mRNA levels. *p < 0.05 compared to control, **p < 0.05 compared to activin A alone, ***p < 0.05 compared to IGF-I alone. Data are mean ± SEM; n = 3 separate experiments. buy flovent inhaler

established; however, given the role of Inh-a in regulating dominant follicle development and preventing ovary sex-cord tumors, our findings could have new implications for understanding the autocrine/paracrine control of folliculogenesis and perhaps ovary tumorigenesis. It is premature to generalize our findings to other activin-dependent phenomena; however, it is not unreasonable to propose that IGF-I might play an important role in the regulation of activin action in other target tissues, both mammalian and nonmammalian.