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乳腺肿瘤高发小鼠中催乳素的代谢:更多转化为不可用免疫测定法检测形式的证据。

Metabolism of prolactin in mice with a high incidence of mammary tumours: evidence for greater conversion into a non-immunoassayable form.

作者信息

Sinha Y N, Baxter S R

出版信息

J Endocrinol. 1979 Jun;81(3):299-314. doi: 10.1677/joe.0.0810299.

DOI:10.1677/joe.0.0810299
PMID:469461
Abstract

Monomeric mouse prolactin containing small amounts of 125I-labelled prolactin was administered to adult female mice of a high (C3H/St) and low (C57BL/St) mammary tumour strain. Their endogenous prolactin had been suppressed with 2-bromo-alpha-ergocryptine. The chromatographic profile, on Sephadex G-100, of prolactin in the serum of mice injected with mouse prolactin was compared by direct measurement (radioactivity count) and by radioimmunoassay (RIA) at several intervals after injection. With both methods, the injected hormone was found in the serum in predominantly two molecular sizes, the so-called 'big' and 'little' forms. Although 'little' prolactin in both strains constituted a constant 80% of the total hormone at most intervals by direct measurement, it comprised a comparatively smaller proportion by RIA. In addition, the RIA-determined 'little' prolactin, after reaching maximum levels at 15 min, progressively decreased with time, the decrease being greater in the C3H/St than in the C57BL/St strain. Similar experiments with mouse growth hormone revealed no such discrepancies between the radioactivity counts and the RIA measurements. A fraction of both 'big' and 'little' forms in the C3H/St strain failed to precipitate completely after the material had been incubated with an antiserum to mouse prolactin. These results demonstrate that the prolactin injected into mice is metabolized in serum into two non-immunoreactive forms, one that elutes with the same elution volume on Sephadex G-100 column as the monomer and the other that elutes as the 'big' form. Furthermore, the loss of immunoreactivity of monomeric mouse prolactin is greater in the high-tumour C3H/St strain than in the low-tumour C57BL/St strain. Endogenous immunoreactive prolactin, on the other hand, was found mainly in the 'big' form in the serum of female mice of the C3H/St strain under basal conditions, whereas it was present only in the 'little' form in comparable mice of the C57BL/St strain, even though pituitary extracts of both strains contained mainly the 'little' form. These results support the concept that monomeric prolactin in the systemic circulation of the tumour-prone C3H/St strain is largely in a non-immunoreactive form.

摘要

将含有少量125I标记催乳素的单体小鼠催乳素注射给高乳腺肿瘤品系(C3H/St)和低乳腺肿瘤品系(C57BL/St)的成年雌性小鼠。它们的内源性催乳素已用2-溴-α-麦角隐亭抑制。在注射小鼠催乳素后的几个时间间隔,通过直接测量(放射性计数)和放射免疫测定(RIA)比较了注射小鼠催乳素的小鼠血清中催乳素在Sephadex G-100上的色谱图谱。两种方法均发现,注射的激素在血清中主要以两种分子大小存在,即所谓的“大”和“小”形式。尽管在大多数时间间隔,通过直接测量,两种品系中的“小”催乳素最多占总激素的80%,但通过RIA测定其占比相对较小。此外,RIA测定的“小”催乳素在15分钟达到最高水平后随时间逐渐减少,C3H/St品系的减少幅度大于C57BL/St品系。对小鼠生长激素进行的类似实验表明,放射性计数与RIA测量之间不存在此类差异。在将C3H/St品系的“大”和“小”形式的物质与抗小鼠催乳素抗血清孵育后,其中一部分未能完全沉淀。这些结果表明,注射到小鼠体内的催乳素在血清中代谢为两种非免疫反应性形式,一种在Sephadex G-100柱上与单体以相同洗脱体积洗脱,另一种以“大”形式洗脱。此外,高肿瘤C3H/St品系中单体小鼠催乳素免疫反应性的丧失比低肿瘤C57BL/St品系更大。另一方面,在基础条件下,C3H/St品系雌性小鼠血清中的内源性免疫反应性催乳素主要以“大”形式存在,而在C57BL/St品系的类似小鼠中仅以“小”形式存在,尽管两个品系的垂体提取物主要含有“小”形式。这些结果支持了这样一种观点,即易患肿瘤的C3H/St品系体循环中的单体催乳素主要处于非免疫反应性形式。

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