Mittal R, Tsutsumi K, Pater A, Pater M M
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Obstet Gynecol. 1993 Jan;81(1):5-12.
To determine the role of the steroid hormones, progesterone and glucocorticoids, and the viral hormone response elements, in the episomal expression of human papillomavirus (HPV) type 16 in primary human ectocervical cells.
In situ hybridization and mutagenesis were used to assess the requirements of these hormones and the HPV 16 glucocorticoid/progesterone response elements in the induction of HPV 16 expression in ectocervical cells.
The assays detected a marked increase in viral messenger RNA only after treatment of the cells with either of the steroid hormones. This response was inhibited by the anti-progestin RU 486 in a concentration-dependent manner. Mutagenesis of the previously identified hormone response element in the regulatory region of the HPV 16 genome had no effect on hormone-induced HPV gene expression. We have now identified two additional hormone response elements. Different combinations of mutations in the three hormone response elements showed that all three were independently sufficient for the hormone-mediated induction of viral transcription.
Steroid hormones induce HPV 16 gene expression in cervical keratinocytes directly through three hormone response elements in the regulatory region of the viral genome. The anti-progestin RU 486 inhibits this induction. Because the physical state of HPV DNA in this in vitro system and in premalignant cervical lesions is extrachromosomal, steroid hormones may have a critical role in modulating HPV expression in such lesions.
确定甾体激素（孕酮和糖皮质激素）以及病毒激素反应元件在人乳头瘤病毒16型（HPV-16）于原代人宫颈外细胞中游离型表达中的作用。
采用原位杂交和诱变技术来评估这些激素以及HPV-16糖皮质激素/孕酮反应元件在宫颈外细胞中诱导HPV-16表达的需求。
检测发现，仅在用任一种甾体激素处理细胞后，病毒信使核糖核酸才有显著增加。抗孕酮药物RU 486以浓度依赖方式抑制了这种反应。对HPV-16基因组调控区中先前鉴定出的激素反应元件进行诱变，对激素诱导的HPV基因表达没有影响。我们现已鉴定出另外两个激素反应元件。这三个激素反应元件中不同的突变组合表明，所有这三个元件对于激素介导的病毒转录诱导都是独立充分的。
甾体激素通过病毒基因组调控区中的三个激素反应元件直接诱导宫颈角质形成细胞中的HPV-16基因表达。抗孕酮药物RU 486抑制这种诱导作用。由于在这个体外系统和癌前宫颈病变中HPV DNA的物理状态是染色体外的，甾体激素可能在调节此类病变中HPV的表达方面起关键作用。
