Mather J P, Roberts P E, Krummen L A
Cell Culture R&D, Genetech, Inc., South San Francisco, CA 94080.
Endocrinology. 1993 Jun;132(6):2732-4. doi: 10.1210/endo.132.6.7684983.
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.
高亲和力激活素结合蛋白，即卵泡抑素，最近已被证明在几种体外系统中可阻断激活素刺激的活性。在本研究中，我们试图扩展这些观察结果，并研究卵泡抑素对激活素在刺激支持细胞单层重聚集和睾丸生殖细胞增殖方面活性的影响，这是通过体外[3H] - 胸腺嘧啶核苷掺入来测定的。用21日龄大鼠制备的生殖细胞 - 支持细胞共培养物分别用单独的培养基或含有重组人（rh）激活素A或rh激活素B的培养基处理，同时添加或不添加卵泡抑素、低亲和力激活素结合蛋白α2巨球蛋白或已知可阻断激活素B活性的单克隆抗体（mAB）。当卵泡抑素与激活素以2倍比例（重量/重量）存在时，它可阻断激活素A刺激支持细胞单层重聚集的能力。然而，在这些相同的培养物中，卵泡抑素对激活素A刺激[3H] - 胸腺嘧啶核苷掺入的能力没有影响。在激活素B处理的培养物中，两种反应均可通过添加针对激活素B的中和性mAB来阻断。这些结果表明，卵泡抑素可以以细胞类型特异性方式调节激活素的作用，并且这种蛋白质可能在调节激活素的生物利用度方面发挥重要作用。
