Luthman M, Wallerman E, Roos P, Werner S
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Acta Endocrinol (Copenh). 1991 Aug;125(2):113-21. doi: 10.1530/acta.0.1250113.
The aim was to investigate the bioactivity of a high-molecular weight human growth hormone, identified following molecular sieve chromatography of serum. Nine patients with pituitary disease and GH insufficiency were studied. All patients had non-detectable levels of immunoreactive GH, less than 0.2 micrograms/l, in diurnal serum profiles. GH bioactivity was determined before and after size-fractionation of serum. The bioassay is based on the finding that a rat lymphoma cell line, Nb2, proliferates in the presence of lactogens. GH and PRL immunoreactivities were measured by radioimmunoassays. Pronounced GH immunoreactivity was found in fractions of sera from 7 out of the 9 patients and of 2 of 4 control sera, particularly in fractions corresponding to the elution volume of high-molecular weight proteins (greater than 160 kD). PRL immunoreactivity was only detected in fractions corresponding to the elution volume of monomeric PRL. Unfractionated serum had a dose-dependent mitogenic effect on the Nb2 cells. GH-antibodies could not inhibit this effect. Fractions of serum obtained from the patients stimulated Nb2 cell division as well. The mitogenic effect of serum fractions could be inhibited by GH-antibodies. Thus, high-molecular weight GH circulating in patients with GH insufficiency were shown to exert a GH-specific bioactivity in vitro after size-fractionation.
目的是研究血清经分子筛层析后鉴定出的一种高分子量人生长激素的生物活性。对9例垂体疾病和生长激素缺乏症患者进行了研究。所有患者日间血清谱中免疫反应性生长激素水平均不可测，低于0.2微克/升。在血清进行大小分级前后测定生长激素生物活性。该生物测定法基于这样一个发现，即大鼠淋巴瘤细胞系Nb2在催乳素存在下会增殖。通过放射免疫测定法测量生长激素和催乳素的免疫反应性。在9例患者中的7例血清以及4例对照血清中的2例血清的组分中发现了明显的生长激素免疫反应性，特别是在对应于高分子量蛋白质洗脱体积（大于160 kD）的组分中。催乳素免疫反应性仅在对应于单体催乳素洗脱体积的组分中检测到。未分级的血清对Nb2细胞有剂量依赖性的促有丝分裂作用。生长激素抗体不能抑制这种作用。从患者获得的血清组分也刺激了Nb2细胞分裂。血清组分的促有丝分裂作用可被生长激素抗体抑制。因此，生长激素缺乏症患者体内循环的高分子量生长激素在大小分级后在体外显示出具有生长激素特异性的生物活性。
