Activin-induced inhibin alpha-subunit production by rat granulosa cells requires endogenous insulin-like growth factor-I.

Published on Mar 1, 1998in Biology of Reproduction3.322
· DOI :10.1095/BIOLREPROD58.3.712
Toshihide Kubo2
Estimated H-index: 2
Shunichi Shimasaki79
Estimated H-index: 79
+ 2 AuthorsGregory F. Erickson66
Estimated H-index: 66
Inhibin-α subunit (Inh-α) gene expression is important for granulosa cell (GC) differentiation and prevention of ovarian tumorigenesis. Studies on Inh-α regulation have implicated activin and insulin-like growth factor-I (IGF-I) in the mechanisms of expression. Here we present evidence that endogenously produced IGF-I plays an obligatory role in activin-induced Inh-α production. Primary cultures of rat GC were incubated with increasing concentrations of various regulatory molecules, and the levels of Inh-α protein and its mRNA were measured in conditioned medium and cells, respectively. Recombinant activin A stimulated Inh-α expression, and the effects were dose- and time-dependent. The receptor tyrosine kinase inhibitor tyrphostin A23 caused a dose-dependent inhibition of activin-dependent Inh-α expression, whereas the inactive isomer, A63, had no effect. The stimulatory effect of activin was also blocked in a dose-dependent manner by added IGF binding protein-4 or -5, and the effects were reversed by IGF-I. Moreover, increasing concentrations of an anti-IGF-I antibody had a similar inhibitory effect on activin-stimulated Inh-α expression. Collectively, these results suggest, for the first time, that endogenously produced IGF-I is required for activin stimulation of Inh-α expression in cultured rat GC.
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