Mercier L, Miller P A, Simons S S
J Steroid Biochem. 1986 Jul;25(1):11-20. doi: 10.1016/0022-4731(86)90275-x.
FU5-5 rat hepatoma (Reuber H35) cells are hypersensitive in that the same percentages of full induction of tyrosine aminotransferase (TAT) occur at much lower concentrations of glucocorticoids than in the related HTC rat hepatoma (Morris) cells. Unexpectedly, these hypersensitive FU5-5 cells also exhibited more agonist activity with the affinity labeling antiglucocorticoids cortisol 21-mesylate and dexamethasone 21-mesylate than did HTC cells (Mercier et al., Endocrinology 112, 601-609 [1983]). In the present study, several other antiglucocorticoids (11-desoxycortisone, progesterone, dexamethasone oxetanone, and RU 486 in addition to dexamethasone 21-mesylate) and the antiandrogen cyproterone acetate were examined to see if chemically unreactive, reversible antisteroids also would exhibit an altered activity (i.e. increased agonist activity) in FU5-5 cells. Each antiglucocorticoid examined did display a 2-fold increased amount of agonist activity in FU5-5 cells, as compared to HTC cells; only RU 486 was predominantly an antagonist in FU5-5 cells but the potency of RU 486 was about 9-fold less than in HTC cells. Dexamethasone, and especially progesterone, was metabolized in FU5-5 and HTC cells. However, differential metabolism in FU5-5 vs HTC cells cannot account for the increased induction of TAT in FU5-5 cells since the amount of agonist activity seen for dexamethasone mesylate (or its metabolites) depended not on the cell type used but rather on the glucocorticoid inducible enzyme monitored, i.e. TAT or glutamine synthetase. The combined data suggest that the hypersensitivity of FU5-5 cells towards glucocorticoid induction of TAT may be linked with the ability of both reversible and irreversible antiglucocorticoids to display increased TAT agonist activity in FU5-5 cells. This behavior was somewhat steroid specific since the antiandrogen cyproterone acetate did not display increased TAT agonist activity in FU5-5 cells compared to HTC cells and was only 2-fold less effective as an antiglucocorticoid in FU5-5.
FU5 - 5大鼠肝癌（鲁伯H35）细胞具有超敏感性，因为与相关的HTC大鼠肝癌（莫里斯）细胞相比，在低得多的糖皮质激素浓度下就能出现相同百分比的酪氨酸转氨酶（TAT）完全诱导。出乎意料的是，这些超敏感的FU5 - 5细胞与HTC细胞相比，对亲和标记抗糖皮质激素甲磺酸皮质醇21酯和甲磺酸地塞米松21酯也表现出更多的激动剂活性（梅西耶等人，《内分泌学》112，601 - 609 [1983]）。在本研究中，除了甲磺酸地塞米松21酯外，还检测了其他几种抗糖皮质激素（11 - 脱氧皮质酮、孕酮、氧杂环丁酮地塞米松和RU 486）以及抗雄激素醋酸环丙孕酮，以观察化学性质不活泼、可逆的抗类固醇在FU5 - 5细胞中是否也会表现出改变的活性（即增加的激动剂活性）。与HTC细胞相比，所检测的每种抗糖皮质激素在FU5 - 5细胞中的激动剂活性确实都增加了2倍；只有RU 486在FU5 - 5细胞中主要是拮抗剂，但RU 486的效力比在HTC细胞中约低9倍。地塞米松，尤其是孕酮，在FU5 - 5和HTC细胞中都发生了代谢。然而，FU5 - 5细胞与HTC细胞之间的差异代谢不能解释FU5 - 5细胞中TAT诱导增加的现象，因为甲磺酸地塞米松（或其代谢产物）的激动剂活性大小不取决于所用的细胞类型，而是取决于所监测的糖皮质激素诱导酶，即TAT或谷氨酰胺合成酶。综合数据表明，FU5 - 5细胞对糖皮质激素诱导TAT的超敏感性可能与可逆和不可逆抗糖皮质激素在FU5 - 5细胞中表现出增加的TAT激动剂活性的能力有关。这种行为在某种程度上具有类固醇特异性，因为与HTC细胞相比，抗雄激素醋酸环丙孕酮在FU5 - 5细胞中没有表现出增加的TAT激动剂活性，并且作为抗糖皮质激素在FU5 - 5细胞中的效力仅比HTC细胞低2倍。
