Activin-attenuated expression of transcripts encoding granulosa cell-derived insulin-like growth factor binding proteins 4 and 5 in the rat: a putative antiatretic effect.

Given the suggestion that intraovarian insulin-like growth factor (IGF)-binding proteins (IGFBPs) may constitute markers of follicular atresia, we investigated the possibility that activin, a putative antiatretic principle, may modulate granulosa cell-derived IGFBPs. Untreated granulosa cells cultured for 72 h exhibited a progressive increase in the steady-state levels of transcripts corresponding to IGFBP-4 and IGFBP-5 (1.5-fold and 12-fold, respectively). Transcript levels corresponding to IGFBP-5 were consistently higher than their IGFBP-4 counterparts. Treatment with activin-A (50 ng/ml) for 72 h produced significant (p IGFBP-4). Activin-B was as effective as activin-A in reducing IGFBP-4 transcripts (31% decrement, p 0.1). No apparent effect was observed for the corresponding proteins. Activin-A action was specific in that treatment with transforming growth factor (TGF)-β 1 , inhibin-A, or Mullerian-inhibiting substance (MIS)-all related peptides-failed to produce statistically significant alterations in the steady-state levels of IGFBP-4 and IGFBP-5 transcripts. Taken together, these observations reveal that activin-A exerts a substantial, relatively rapid, follistatin-neutralizable, dose- and time-dependent inhibitory effect on granulosa cell-derived IGFBP transcripts (IGFBP-5 > IGFBP-4). Other members of the TGFβ superfamily (e.g., inhibin-A, TGFβ 1 , and MIS) were without significant effect on the expression of IGFBP-4 and IGFBP-5. To the extent that the inhibition of IGFBP-4 and IGFBP-5 expression is associated with, and possibly causally related to, the promotion of follicular health, the present observations are in keeping with the proposition that activin may play an antiatretic role in the dynamic process of follicular selection.