The molecular nature of circulating growth hormone in normal and acromegalic man: evidence for a principal and minor monomeric forms.

The molecular nature of circulating growth hormone in normal and acromegalic man: evidence for a principal and minor monomeric forms.
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正常和肢端肥大症男性循环生长激素的分子性质:主要和次要单体形式的证据。

DOI:
10.1210/jcem-56-5-946
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发表时间:
1983
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
K. Amburn
K. Amburn
中科院分区:
--
文献类型:
--
作者:
G. Baumann;J. Maccart;K. Amburn

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从垂体中提取的人类生长激素 (hGH) 由多种分子形式组成。单体垂体形式包括单链 22,000 道尔顿多肽(22K;hGH-B)、具有 15 个氨基酸缺失的 20,000 道尔顿变体(20K)、3 种蛋白水解裂解的 2 链形式(hGH-C、-D 和 -E)、2 种脱酰胺形式、乙酰化形式(快速 hGH)和其他仅部分表征的形式。目前尚不清楚这些形式中哪一种是分泌的,也不知道循环 hGH 的确切性质是什么。为了回答这些问题,我们从左旋多巴刺激 hGH 分泌后的正常志愿者和肢端肥大症患者的血浆置换获得的人血浆中提取了 hGH。我们通过免疫吸附色谱法提取和浓缩 hGH,并在天然和变性(十二烷基硫酸钠和尿素)、非还原和还原(二硫苏糖醇)条件下通过聚丙烯酰胺凝胶电泳以及等电聚焦检查其化学性质。在所有情况下,血浆中 hGH 的主要形式是 22K,约占所有免疫反应性 hGH 的 85%。此外,我们还发现了 20K 作为次要形式(约占所有 hGH 的 7%)和一种或多种酸性形式(N-乙酰化、脱酰胺或裂解 hGH;占所有 hGH 的 5-10%)存在的证据。不可能准确鉴定酸性形式。然而,高生物活性的裂解形式 hGH-D 和 -E 被认为是不可检测的(少于所有 hGH 的 5%)。我们得出的结论是:1) hGH 的几种单体分子形式在正常人和肢端肥大症患者体内循环; 2) 循环 hGH 形式的模式部分反映了它们在垂体中的相对流行率; 3) 在血液中检测不到具有增强生物活性的蛋白水解裂解的 2 链 hGH 形式; 4) 肢端肥大症中循环的单体 hGH 在质量上与正常 hGH 没有区别。
Human GH (hGH) extracted from pituitary glands consists of several molecular forms. Monomeric pituitary forms include the single chain 22,000-dalton polypeptide (22K; hGH-B), a 20,000-dalton variant with a 15-amino acid deletion (20K), 3 proteolytically cleaved 2-chain forms (hGH-C, -D, and -E), 2 deamidated forms, an acetylated form (fast hGH), and other, only partially characterized forms. It is not known which of these forms is secreted, nor what the precise nature of circulating hGH is. To answer these questions, we have extracted hGH from human plasma obtained by plasmapheresis from normal volunteers after L-dopa stimulation of hGH secretion and from acromegalic patients. We extracted and concentrated hGH by immunoadsorbent chromatography and examined its chemical nature by polyacrylamide gel electrophoresis under native and denaturing (sodium dodecyl sulfate and urea), nonreducing and reducing (dithiothreitol) conditions as well as by isoelectric focusing. In all cases, the predominant form of hGH present in plasma was 22K, which accounted for approximately 85% of all immunoreactive hGH. In addition, we found evidence for the presence of 20K as a minor form (approximately 7% of all hGH) and of one or more acidic forms (N-acetylated, deamidated, or cleaved hGH; 5-10% of all hGH). Exact identification of the acidic form(s) was not possible. However, the highly bioactive cleaved forms hGH-D and -E were judged to be undetectable (less than 5% of all hGH). We conclude that 1) several monomeric molecular forms of hGH circulate in normal and acromegalic man; 2) the pattern of circulating hGH forms reflects in part their relative prevalence in the pituitary gland; 3) proteolytically cleaved 2-chain hGH forms with enhanced bioactivity are not detectable in blood; and 4) monomeric hGH circulating in acromegaly is qualitatively indistinguishable from normal hGH.
人类生长激素 DNA 序列和 mRNA 结构:可能的选择性剪接。
DOI: 10.1093/nar/9.15.3719
发表时间: 1981
影响因子: 14.9
作者:
DeNoto,FM;Moore,DD;Goodman,HM
通讯作者: Goodman,HM