FOLLISTATIN MODULATES ACTIVIN ACTIVITY IN A CELL-SPECIFIC AND TISSUE-SPECIFIC MANNER

The high affinity activin-binding protein, follistatin, has recently b een shown to block activin-stimulated activites in several in vitro sy stems. In the present study we sought to extend these observations and investigate the effects of follistatin on the activity of activin in stimulating the re-aggregation of Sertoli cell monolayers and prolifer ation of testicular germ cells, as measured by incorporation of [3H]-t hymidine in vitro. Germ-Sertoli cell cocultures prepared from 21 day o ld rats were treated with media alone or media containing recombinant human (rh) activin A or rh activin B with or without follistatin, the low affinity activin-binding protein, alpha2 macroglobulin, or a moncl onal antibody (mAB) known to block activin B activity. Follistatin blo cked the ability of activin A to stimulate reaggregation of Sertoli ce ll monolayers when present at a 2-fold ratio (wt/wt) to activin. Howev er, in these same cultures, follistatin had no effect on the ability o f activin A to stimulate [3H]-thymidine incorporation. In activin B-tr eated cultures, both responses could be blocked by the addition of a n eutralizing mAB directed against activin B. These results suggest that follistatin can modulate activin action in a cell-type specific fashi on, and that this protein may play an important role in regulating the bioavailablility of activin.