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大鼠垂体产后发育过程中促肾上腺皮质激素原/内啡肽衍生肽的翻译后加工

Posttranslational processing of proadrenocorticotropin/endorphin-derived peptides during postnatal development in the rat pituitary.

作者信息

Sato S M, Mains R E

出版信息

Endocrinology. 1985 Aug;117(2):773-86. doi: 10.1210/endo-117-2-773.

DOI:10.1210/endo-117-2-773
PMID:2990862
Abstract

The anterior pituitary content of pro-ACTH/endorphin-related peptides increased 5-fold from birth to 4 weeks and increased another 3-fold by adulthood. In contrast, the neurointermediate lobe content of pro-ACTH/endorphin-related peptides increased 15-fold from birth to 4 weeks and another 10-fold by adulthood. Despite the dramatic increase in content, posttranslational processing of pro-ACTH/endorphin in the neurointermediate lobe of the neonate closely resembled intermediate lobe processing in the adult; alpha MSH- and beta-endorphin-sized molecules (rather than ACTH and beta-lipotropin) accounted for more than 90% of the immunoreactivity in both neonates and adults. In the neurointermediate pituitary of both the neonate and the adult, the alpha MSH-sized material was largely diacetylated, and the beta-endorphin was both alpha-N-acetylated and C-terminally shortened. However, the extent of C-terminal shortening of beta-endorphin in the neurointermediate lobe of the neonate was not as great as that observed by postnatal day 21 or that in the adult. In the anterior pituitary, distinct differences in processing occurred between birth and adulthood. Proteolytic processing of pro-ACTH/endorphin was not as extensive on day 1 as in the adult, and pro-ACTH/endorphin accounted for 40-50% of the total immunoreactive peptide. The extent of processing of precursor increased around day 21, and a higher percentage of ACTH-(1-39) and beta-endorphin-(1-31)-sized material was found. Neonatal anterior pituitary contained substantial amounts of alpha MSH-sized material, whereas in adult anterior pituitary, less than 1-2% of the ACTH-related material was alpha MSH-sized. Despite these differences in the extent of proteolytic processing, neonatal anterior pituitary corticotropes resembled those of adults, in that they did not alpha-N-acetylate beta-endorphin or alpha MSH. Immunocytochemical studies demonstrated that a subset of the neonatal anterior pituitary corticotropes produced alpha MSH-related molecules.

摘要

促肾上腺皮质激素原/内啡肽相关肽在前叶垂体中的含量从出生到4周增加了5倍,到成年时又增加了3倍。相比之下,促肾上腺皮质激素原/内啡肽相关肽在神经中间叶的含量从出生到4周增加了15倍,到成年时又增加了10倍。尽管含量急剧增加,但新生儿神经中间叶中促肾上腺皮质激素原/内啡肽的翻译后加工与成体中间叶的加工非常相似;α-促黑素(α-MSH)和β-内啡肽大小的分子(而非促肾上腺皮质激素和β-促脂素)在新生儿和成人中均占免疫反应性的90%以上。在新生儿和成人的神经中间叶垂体中,α-MSH大小的物质大多为双乙酰化,β-内啡肽则为α-N-乙酰化且C末端缩短。然而,新生儿神经中间叶中β-内啡肽C末端缩短的程度不如出生后第21天或成体中观察到的程度大。在前叶垂体中,出生和成年之间的加工存在明显差异。出生第1天时,促肾上腺皮质激素原/内啡肽的蛋白水解加工不如成体广泛,促肾上腺皮质激素原/内啡肽占总免疫反应性肽的40%-50%。前体加工程度在第21天左右增加,发现了更高比例的促肾上腺皮质激素(1-39)和β-内啡肽(1-31)大小的物质。新生儿前叶垂体含有大量α-MSH大小的物质,而在成体前叶垂体中,与促肾上腺皮质激素相关的物质中小于1%-2%为α-MSH大小。尽管蛋白水解加工程度存在这些差异,但新生儿前叶垂体促肾上腺皮质激素细胞与成体相似,即它们不会对β-内啡肽或α-MSH进行α-N-乙酰化。免疫细胞化学研究表明,新生儿前叶垂体促肾上腺皮质激素细胞的一个亚群产生α-MSH相关分子。

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