Schachtschabel D O, Sluke G
Z Gerontol. 1986 May-Jun;19(3):173-8.
Continuous (long-term) exposure of cultured normal (diploid) human fibroblasts (WI-38) to hydrocortisone (1.4 X 10(-7) M) resulted, as originally described by Macieira-Coelho (1966) and Cristofalo (1970), in a stimulation of proliferative activity and an increase of population doublings. Stimulation of DNA-synthesis by hydrocortisone, as measured by 3H-thymidine incorporation, required the presence of serum in the culture medium. Analysis of the cellular glycosaminoglycan (GAG) pattern, as measured by 14C-glucosamine incorporation into the various GAG types (hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate) revealed a significant increase of cell-bound hyaluronic acid (it appears to be predominantly located at the cell surface or pericellular, since it is removable to a large extent by trypsin treatment), while the distribution pattern of sulfated GAGs did not exhibit a significant change. This increase of cellular hyaluronic acid synthesis was regarded largely as an adaptive response to hydrocortisone, since its removal from the culture medium of hydrocortisone pretreated cultures resulted in a significant decrease of cellular hyaluronic acid. Possible functions of cell-bound hyaluronic acid were suggested in regard to cell surface properties (cell-cell and cell-substratum adhesion; migratory activity). Thus, decreased adhesiveness (by elevated cellular hyaluronic acid) might be a decisive factor for the well-known increase in cell saturation density caused by hydrocortisone. Generally, the present findings support a concept (Sluke et al., 1981; Schachtschabel and Sluke, 1984) that an increase of cellular hyaluronic acid synthesis is "growth-favorable", which is in line with previous findings of a decrease of hyaluronic acid synthesis by growth restriction in the course of in vitro ageing (Sluke et al., 1981).
如Macieira - Coelho（1966年）和Cristofalo（1970年）最初所描述的那样，将培养的正常（二倍体）人成纤维细胞（WI - 38）长期持续暴露于氢化可的松（1.4×10⁻⁷M）中，会刺激增殖活性并增加群体倍增次数。通过³H - 胸腺嘧啶核苷掺入法测定，氢化可的松对DNA合成的刺激作用需要培养基中存在血清。通过将¹⁴C - 葡糖胺掺入各种糖胺聚糖类型（透明质酸、硫酸乙酰肝素、硫酸软骨素、硫酸皮肤素）来分析细胞糖胺聚糖（GAG）模式，结果显示细胞结合的透明质酸显著增加（由于它在很大程度上可被胰蛋白酶处理去除，所以似乎主要位于细胞表面或细胞周缘），而硫酸化GAG的分布模式没有显著变化。细胞透明质酸合成的这种增加在很大程度上被视为对氢化可的松的一种适应性反应，因为从预先用氢化可的松处理的培养物的培养基中去除它会导致细胞透明质酸显著减少。关于细胞表面特性（细胞 - 细胞和细胞 - 基质粘附；迁移活性），有人提出了细胞结合透明质酸的可能功能。因此，（由于细胞透明质酸升高导致的）粘附性降低可能是氢化可的松引起的细胞饱和密度众所周知的增加的一个决定性因素。一般来说，目前的研究结果支持一种观点（Sluke等人，1981年；Schachtschabel和Sluke，1984年），即细胞透明质酸合成的增加是“有利于生长的”，这与之前关于体外衰老过程中生长受限导致透明质酸合成减少的研究结果一致（Sluke等人，1981年）。
