Molecular mechanisms regulating ACTH synthesis and release.

Molecular mechanisms regulating ACTH synthesis and release.
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调节 ACTH 合成和释放的分子机制。

DOI:
10.1111/j.1749-6632.1987.tb24960.x
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发表时间:
1987
影响因子:
5.2
通讯作者:
Reisine,T
Reisine,T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Thermos,K;Reisine,T

文献摘要

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下丘脑促肾上腺皮质激素释放因子(CRF)是垂体前叶促肾上腺皮质激素细胞的重要生理调节因子。CRF刺激促肾上腺皮质激素(ACTH)的释放,在体内和在玻璃体中。此外,它通过增加前激素阿黑皮素原(POMC)的产生来增强ACTH的合成。细胞类型的异质性和低密度的促肾上腺皮质激素分泌细胞在垂体前叶阻碍了精确的分子事件的CRF引起促肾上腺皮质激素释放的确定。小鼠垂体前叶细胞系AtT-20由ACTH分泌细胞的同质群体组成。“像正常的促肾上腺皮质激素细胞一样,AtT-20细胞通过分泌免疫反应性ACTH和β-内啡肽来对合成CRF作出反应。“CRF类似物在从AtT-20细胞释放ACTH方面显示出与在培养的垂体前叶细胞中观察到的效力相同的等级顺序。此外,糖皮质激素阻断CRF刺激的ACTH从AtT-20细胞以及垂体前叶的原代培养物释放。由于AtT-20细胞是同质的,可以高密度生长,并通过释放ACTH对CRF作出反应,因此AtT-20细胞已用作研究CRF引发的细胞事件以引起激素分泌的模型系统。
The hypothalamic peptide corticotropin releasing factor (CRF) is an important physiological regulator of anterior pituitary corticotrophs. CRF stimulates the release of adrenocorticotropin (ACTH) in vivo', 2 and in vitragP Furthermore, it potentiates ACTH synthesis by increasing the production of the prohormone proopiomelanocortin (POMC) in the anteriorStudies directed towards the understanding of the molecular mechanisms by which CRF evokes ACTH secretion from the pituitary have mainly utilized primary cultures of the rat adenohyp~ physis.~.~ The heterogeneity of the cell types and the low density of the ACTH-secreting cells in the anterior pituitary have hampered the determination of the precise molecular events initiated by CRF to evoke ACTH release. The mouse anterior pituitary cell line AtT-20 consists of a homogeneous population of ACTH-secreting cells." Like normal corticotrophs, AtT-20 cells respond to synthetic CRF by secreting immunoreactive ACTH and beta-endorphin." Analogues of CRF show the same rank order of potency in releasing ACTH from AtT-20 cells as observed in anterior pituitary cells in culture. Furthermore, glucocorticoids block CRF-stimulated ACTH release from AtT-20 cells as well as primary cultures of the anterior pituitary. Because they are homogeneous, can be grown in high density and respond to CRF by releasing ACTH, AtT-20 cells have served as a model system for studying the cellular events triggered by CRF to evoke hormone secretion.