Presence and characterization of the somatostatin precursor in normal human pituitaries and in growth hormone secreting adenomas.

Presence and characterization of the somatostatin precursor in normal human pituitaries and in growth hormone secreting adenomas.
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正常人垂体和生长激素分泌腺瘤中生长抑素前体的存在和特征。

DOI:
10.1210/jcem.76.1.8093621
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发表时间:
1993
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
Dominique Joubert
Dominique Joubert
中科院分区:
--
文献类型:
--
作者:
Laurence Levy;J. Bourdais;B. Mouhieddine;C. Benlot;S. Villares;P. Cohen;Françoise Peillon;Dominique Joubert

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正常和肿瘤的人垂体在体外释放SRIH并含有编码preproSRIH的信使RNA。在本研究中,我们记录了人类正常垂体和生长激素分泌腺瘤中SRIH前体的存在和特征。正常垂体和腺瘤酸提取物的分子筛过滤显示存在三个免疫反应性SRIH峰,不同于SRIH 1-28和SRIH 1-14。在非还原和还原条件下进行的蛋白质印迹分析证实存在三种不同的免疫反应性形式,其分子量分别估计为21、17和12千道尔顿。当在反相高效液相色谱中分析时,三个峰中含有的三种免疫反应性SRIH物质与从大鼠下丘脑和从用人preproSRIH互补DNA转染的神经母细胞瘤细胞系(N2 A)中提取的proSRIH共洗脱。这三种形式都不能与伴刀豆球蛋白A结合。用特异性内肽酶消化这三种形式导致产生SRIH 1-14,表明它们可以被认为是SRIH前体或相关形式。分子筛过滤后proSRIH量的估计表明,正常人垂体(n = 4)含有可变量的proSRIH(26.5-303 pg/mg蛋白质),除了SRIH 1-28之外,还总是存在21-、17-和12-千道尔顿形式。相比之下,在测试的21个腺瘤中,仅11个含有proSRIH物质(9-4480 pg/mg蛋白质)。此外,SRIH 1-28和SRIH 1-14在这些腺瘤中均未检测到。这些数据表明在正常垂体中存在高分子量SRIH,其代表未加工的proSRIH物质。这为SRIH的局部合成提供了额外的论据。此外,只有50%的GH分泌型垂体腺瘤中含有专门的proSRIH,这一事实可能反映了信使RNA翻译或proSRIH加工或两者的改变,导致这些腺瘤中缺乏成熟的SRIH。
Normal and tumoral human pituitaries release in vitro SRIH and contain messenger RNAs encoding preproSRIH. In the present study, we document the presence and characterization of the SRIH precursor in both human normal pituitaries and in GH-secreting adenomas. Molecular sieve filtration of normal pituitary and adenoma acid extracts revealed the presence of three immunoreactive SRIH peaks, distinct from SRIH 1-28 and SRIH 1-14. Western blot analysis performed under both nonreducing and reducing conditions confirmed the presence of the three different immunoreactive forms with respective molecular masses estimated as 21, 17, and 12 kilodaltons. When analyzed in reverse phase high performance liquid chromatography, the three immunoreactive SRIH material contained in the three peaks coeluted with the proSRIH extracted from rat hypothalamus and from a neuroblastoma cell line (N2A) transfected with the human preproSRIH complementary DNA. None of these three forms could bind concanavalin A. Digestion of the three forms with a specific endopeptidase resulted in the generation of SRIH 1-14, indicating that they can be considered as SRIH precursor or related forms. Estimation of proSRIH amount after molecular sieve filtration indicated that normal human pituitaries (n = 4) contained proSRIH in variable amounts (from 26.5-303 pg/mg proteins), the 21-, 17-, and 12-kilodalton forms being always present, in addition to SRIH 1-28. In contrast, among the 21 adenomas tested, only 11 contained proSRIH material (from 9-4480 pg/mg proteins). Moreover, neither SRIH 1-28 nor SRIH 1-14 could be detected in these adenomas. These data demonstrate the presence of high molecular mass SRIH in normal pituitaries which represent unprocessed proSRIH material. This provides an additional argument for a local synthesis of SRIH. Additionally, the fact that only 50% of GH-secreting pituitary adenomas here studied contain exclusively proSRIH may reflect an alteration in messenger RNA translation or in proSRIH processing, or both, resulting in the absence of mature SRIH in these adenomas.
甲状腺激素调节大鼠垂体前叶的血管活性肠肽 (VIP) mRNA 水平。
DOI: 10.1210/endo-125-4-2221
发表时间: 1989
期刊: Endocrinology
影响因子: 4.8
作者:
Segerson,TP;Lam,KS;Cacicedo,L;Minamitani,N;Fink,JS;Lechan,RM;Reichlin,S
通讯作者: Reichlin,S