Castellano T J, Schiffman R L, Jacob M C, Loeb J N
Endocrinology. 1978 Apr;102(4):1107-12. doi: 10.1210/endo-102-4-1107.
The influence of glucocorticoid hormone on the time-course of liver regeneration in the immature rat has been studied by direct measurement of the rate of DNA accretion after the stimulus of partial hepatectomy. In contrast to hepatocyte proliferation associated with normal growth, which almost completely abolished by small doses of glucocorticoid, it is shown that even enormous amounts of hormone produce, at most, about a halving of the intrinsic cell proliferation rate in regenerating liver. Although deceptively magnified by the exponential growth pattern of the hepatic remnant, the inhibition of cell proliferation is thus considerably less complete than that induced in normally growing liver by much lower doses of hormone, a finding at distinct variance with the conclusions of earlier studies based entirely upon observations of radioactive precursor incorporation rather than direct measurement of DNA accretion. The mechanism by which a regenerative stimulus causes hepatocyte proliferation to lose its normal sensitivity to suppression by glucocorticoid, and thereby to exhibit a steroid insensitivity characteristic of other tissues in which cell proliferation reflects cell replenishment rather than normal growth, remains unknown.
通过直接测量部分肝切除刺激后DNA增加速率，研究了糖皮质激素对未成熟大鼠肝脏再生时间进程的影响。与正常生长相关的肝细胞增殖不同，小剂量糖皮质激素几乎能完全抑制正常生长相关的肝细胞增殖，而研究表明，即使大量激素最多也只能使再生肝脏中的固有细胞增殖速率减半。尽管肝残余物的指数生长模式会使这种抑制作用看似被放大，但细胞增殖的抑制程度远不如低得多的激素剂量在正常生长肝脏中所诱导的那样完全，这一发现与早期完全基于放射性前体掺入观察而非DNA增加直接测量得出的结论明显不同。再生刺激导致肝细胞增殖失去对糖皮质激素抑制的正常敏感性，从而表现出其他组织中细胞增殖反映细胞补充而非正常生长时所特有的类固醇不敏感性的机制仍然未知。
