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.