生长激素与药物代谢。对核糖核酸聚合酶活性和染色质的急性影响。

Growth hormone and drug metabolism. Acute effects on nuclear ribonucleic acid polymerase activity and chromatin.

作者信息

Spelsberg T C, Wilson J T

出版信息

Biochem J. 1976 Feb 15;154(2):439-48. doi: 10.1042/bj1540439.

DOI:10.1042/bj1540439

PMID:945734

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1172725/

Abstract

Adult male rats, subjected either to sham operation or to hypophysectomy and adrenalectomy were maintained for 10 days before treatment with growth hormone. Results of the acute effects of growth hormone on the rat liver nuclear RNA polymerase I (nucleolar) and II (nucleoplasmic) activities as well as the chromatin template capacity were then studied and compared with the growth-hormone effects on the drug metabolism described in the preceding paper (Wilson & Spelsberg, 1976). 2. Conditions for isolation and storage of nuclei for maintenance of optimal polymerase activities are described. It is verified that the assays for polymerase activities require a DNA template, all four nucleoside triphosphates, and a bivalent cation, and that the acid-insoluble radioactive product represents RNA. Proof is presented that under high-salt conditions DNA-like RNA (polymerase II) is synthesized, and that under low-salt conditions in the presence of alpha-amanitin, rRNA (polymerase I) is synthesized. 3. In the livers of hypophysectomized/adrenalectomized rats, growth hormone increases the activity of both RNA polymerase enzymes and the chromatin template capacity within 1h after treatment. The effects last for 12h in the case of polymerase II but for only 6h in the case of polymerase I. Sham-operated rats respond to growth hormone in a manner somewhat similar to that shown by hypophysectomized/adrenalectomized rats. These results, which demonstrate an enhancement of RNA polymerase I activity in response to growth hormone, support those from other laboratories. 4. Growth-hormone enhancement of the chromatin template capacity in the liver of hypophysectomized/adrenalectomized rats contrasts with previous reports. The growth-hormone-induced de-repression of the chromatin DNA could represent the basis of the growth-hormone-induced enhancement of RNA polymerase II activity in the hypophysectomized/adrenalectomized rats, although some effect of growth-hormone on the polymerase enzymes is still suggested.

摘要

成年雄性大鼠，接受假手术或垂体切除及肾上腺切除术后，在给予生长激素治疗前维持10天。然后研究生长激素对大鼠肝细胞核RNA聚合酶I（核仁）和II（核质）活性以及染色质模板能力的急性影响，并与前文（Wilson & Spelsberg，1976）中所述的生长激素对药物代谢的影响进行比较。2. 描述了分离和储存细胞核以维持最佳聚合酶活性的条件。已证实，聚合酶活性测定需要DNA模板、所有四种核苷三磷酸和二价阳离子，且酸不溶性放射性产物代表RNA。有证据表明，在高盐条件下合成DNA样RNA（聚合酶II），在低盐条件下且存在α-鹅膏蕈碱时合成rRNA（聚合酶I）。3. 在垂体切除/肾上腺切除的大鼠肝脏中，生长激素在治疗后1小时内增加了两种RNA聚合酶的活性以及染色质模板能力。聚合酶II的作用持续12小时，而聚合酶I的作用仅持续6小时。假手术大鼠对生长激素的反应方式与垂体切除/肾上腺切除大鼠的反应方式有些相似。这些结果表明生长激素可增强RNA聚合酶I的活性，支持了其他实验室的研究结果。4. 生长激素增强垂体切除/肾上腺切除大鼠肝脏染色质模板能力的结果与先前的报道形成对比。生长激素诱导的染色质DNA去抑制可能是垂体切除/肾上腺切除大鼠中生长激素诱导的RNA聚合酶II活性增强的基础，尽管仍提示生长激素对聚合酶有一定作用。