Hornsby P J
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
Endocr Res. 1991;17(1-2):109-34. doi: 10.1080/07435809109027192.
Over long periods of growth in culture, bovine adrenocortical cells lose the ability to express the steroid hydroxylase genes. For 17 alpha-hydroxylase, cells show a stochastic pattern of phenotypic switching from a state in which they express this gene in response to cyclic AMP to a state in which the gene is no longer inducible. Introducing SV40 T antigen into bovine adrenocortical cells greatly increases their replicative potential; steroid hydroxylase expression in these clones resembles that of the precursor cells before transfection. The other steroid hydroxylases (21-hydroxylase and 11 beta-hydroxylase) appear to undergo phenotypic switching like 17 alpha-hydroxylase. The loss of expression of these genes appears to be more rapid, but there are differences in the requirements of 21-hydroxylase and 11 beta-hydroxylase versus 17 alpha-hydroxylase for induction by cyclic AMP; additionally, growth of cells in extracellular matrix Matrigel was required for expression of 21-hydroxylase and 11 beta-hydroxylase in long-term cultures of either normal or SV40 T antigen-transfected cells. Understanding the molecular basis for the phenotypic switching of steroid hydroxylases that occurs in bovine adrenocortical cells may elucidate mechanisms for cellular senescence and for maintenance of tissue-specific functions during long-term growth in culture.
在长期的培养生长过程中，牛肾上腺皮质细胞失去了表达类固醇羟化酶基因的能力。对于17α-羟化酶，细胞表现出一种表型转换的随机模式，从它们响应环磷酸腺苷（cAMP）表达该基因的状态转变为该基因不再可诱导的状态。将SV40 T抗原导入牛肾上腺皮质细胞大大增加了它们的复制潜能；这些克隆中的类固醇羟化酶表达类似于转染前前体细胞的表达。其他类固醇羟化酶（21-羟化酶和11β-羟化酶）似乎像17α-羟化酶一样经历表型转换。这些基因表达的丧失似乎更快，但21-羟化酶和11β-羟化酶与17α-羟化酶在由环磷酸腺苷诱导方面的要求存在差异；此外，在正常或SV40 T抗原转染细胞的长期培养中，21-羟化酶和11β-羟化酶的表达需要细胞在细胞外基质基质胶中生长。了解牛肾上腺皮质细胞中发生的类固醇羟化酶表型转换的分子基础，可能有助于阐明细胞衰老机制以及在长期培养生长过程中组织特异性功能的维持机制。
