Stewart J K, Reagan C R, Kostyo J L
Endocrinology. 1977 May;100(5):1376-83. doi: 10.1210/endo-100-5-1376.
Growth hormone-like activity was demonstrated in diluted plasma of rats bearing the GH-secreting tumor, MtTW15, using an in vitro bioassay. The bioassay used depends upon the ability of GH in vitro to stimulate the uptake of 3-0-methyl glucose (3-OMG) into the isolated diaphragm of the hypophysectomized rat. It was found that the effect of the diluted plasma on this system was qualitatively like that of rat pituitary GH. Theophylline, a drug which blocks the action of GH on 3-OMG uptake by the diaphragm but has no effect on the actions of insulin or somatomedin on this process, completely abolished the stimulatory action of the plasma on the transport of the sugar. Furthermore, antibodies against rat pituitary GH (ArGH) completely abolished the biological activity of the diluted plasma. When plasma was diluted to give specific concentrations of rat GH (rGH), as determined by radioimmunoassay (RIA), the plasma produced responses in the 3-OMG assay equivalent to those obtained with similar concentrations of pituitary rGH. A good correlation was also observed between the concentration of rGH in the plasma of tumor-bearing rats measured by RIA and by an in vivo bioassay in which the effects were determined of injections of diluted plasma into hypophysectomized rats on the subsequent incorporation of [3H]thymidine into costal cartilage. This in vivo biological activity was abolished by incubation of the plasma with ArGH prior to its injection into the test animals. Thus, these studies indicate that in rats bearing the MtTW15 tumor there is a good correlation between the biological and immunological activities of the rGH circulating the bloodstream.
采用体外生物测定法,在携带分泌生长激素(GH)的肿瘤MtTW15的大鼠稀释血浆中证实了生长激素样活性。所使用的生物测定法取决于体外GH刺激3-0-甲基葡萄糖(3-OMG)摄取到垂体切除大鼠分离膈肌中的能力。发现稀释血浆对该系统的作用在性质上与大鼠垂体GH的作用相似。茶碱是一种阻断GH对膈肌摄取3-OMG作用但对胰岛素或生长调节素在此过程中的作用无影响的药物,它完全消除了血浆对糖转运的刺激作用。此外,抗大鼠垂体GH抗体(ArGH)完全消除了稀释血浆的生物活性。当血浆稀释至通过放射免疫测定(RIA)确定的特定大鼠GH(rGH)浓度时,血浆在3-OMG测定中产生的反应与用类似浓度的垂体rGH获得的反应相当。通过RIA测定的荷瘤大鼠血浆中rGH浓度与通过体内生物测定法(在该测定法中确定将稀释血浆注射到垂体切除大鼠中对随后[3H]胸苷掺入肋软骨的影响)之间也观察到良好的相关性。在将血浆注射到试验动物之前,用ArGH孵育血浆可消除这种体内生物活性。因此,这些研究表明,在携带MtTW15肿瘤的大鼠中,循环血液中的rGH的生物学活性和免疫活性之间存在良好的相关性。