Follistatin modulates activin activity in a cell- and tissue-specific manner.
The high affinity activin-binding protein, follistatin, has recently been shown to block activin-stimulated activities in several in vitro systems. 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 proliferation of testicular germ cells, as measured by incorporation of [3H]-thymidine in vitro. Germ-Sertoli cell cocultures prepared from 21 day old 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, alpha 2 macroglobulin, or a monoclonal antibody (mAB) known to block activin B activity. Follistatin blocked the ability of activin A to stimulate reaggregation of Sertoli cell monolayers when present at a 2-fold ratio (wt/wt) to activin. However, in these same cultures, follistatin had no effect on the ability of activin A to stimulate [3H]-thymidine incorporation. In activin B-treated cultures, both responses could be blocked by the addition of a neutralizing mAB directed against activin B. These results suggest that follistatin can modulate activin action in a cell-type specific fashion, and that this protein may play an important role in regulating the bioavailability of activin.
Mather
J P
JP
Cell Culture R&D, Genetech, Inc., South San Francisco, CA 94080.
Roberts
P E
PE
Krummen
L A
LA
D028341:Activins; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003584:Cytological Techniques; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D038681:Follistatin; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D007265:Inhibins / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000494:pharmacology
D038681:Follistatin; D006023:Glycoproteins; D000511:alpha-Macroglobulins; D028341:Activins; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D013936:Thymidine