Basile D P, Holzwarth M A
Department of Physiology and Biophysics, University of Illinois, Urbana 61801.
Am J Physiol. 1993 Dec;265(6 Pt 2):R1253-61. doi: 10.1152/ajpregu.1993.265.6.R1253.
We have investigated the role of basic fibroblast growth factor (bFGF) in the neurally mediated compensatory adrenal growth response. Unilateral adrenalectomy resulted in a 13, 6, and 22% increase in adrenal weight, protein, and DNA content, respectively, and 33-40% increases in the rate of cell proliferation measured by [3H]thymidine incorporation in vitro. Three forms of bFGF, approximately 18.6, 21, and 22.5 kDa, were identified in rat adrenals by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. bFGF was localized immunocytochemically in cells of the glomerulosa and the medulla. bFGF stimulated a 68-80% increase in the rate of DNA synthesis in adrenal capsule-glomerulosa preparations in vitro. Suramin (0.1 mM), a growth factor antagonist, blocked bFGF receptor interaction in vitro and, at 200 mg/kg given 5-7 days before adrenal surgery, blocked compensatory growth. Conversely, at 2.0 mg/kg, suramin significantly enhanced the compensatory growth response, perhaps caused by suramin-induced bFGF receptor upregulation, since suramin pretreatment also enhanced DNA synthesis in response to exogenous bFGF in vitro. These results suggest that bFGF may mediate proliferation in the compensatory adrenal growth response.
我们研究了碱性成纤维细胞生长因子(bFGF)在神经介导的代偿性肾上腺生长反应中的作用。单侧肾上腺切除术后,肾上腺重量、蛋白质和DNA含量分别增加了13%、6%和22%,通过体外[3H]胸腺嘧啶核苷掺入法测定的细胞增殖速率增加了33%-40%。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和蛋白质印迹法在大鼠肾上腺中鉴定出三种形式的bFGF,分子量分别约为18.6、21和22.5 kDa。免疫细胞化学法显示bFGF定位于球状带和髓质的细胞中。bFGF可刺激体外肾上腺被膜-球状带制剂中DNA合成速率提高68%-80%。生长因子拮抗剂苏拉明(0.1 mM)在体外可阻断bFGF受体相互作用,在肾上腺手术前5-7天给予200 mg/kg时可阻断代偿性生长。相反,给予2.0 mg/kg时,苏拉明可显著增强代偿性生长反应,这可能是由于苏拉明诱导的bFGF受体上调所致,因为苏拉明预处理也可增强体外对外源性bFGF的DNA合成反应。这些结果表明,bFGF可能介导代偿性肾上腺生长反应中的细胞增殖。