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miR-7 介导了 NE 影响猪垂体中 FSH 和 LH 合成的信号通路。

miR-7 mediates the signaling pathway of NE affecting FSH and LH synthesis in pig pituitary.

机构信息

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China.

出版信息

J Endocrinol. 2020 Mar;244(3):459-471. doi: 10.1530/JOE-19-0331.

Abstract

MicroRNA-7 (miR-7) is an important modulator of a plenty of gene expressions and the interrelated biological processes, highly expressed in porcine pituitary. Norepinephrine (NE), acting as an important neurotransmitter or/and a hormone secreted excessively under stress, affects the synthesis and secretion of various hormones, including pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are the key hormones which regulate sexual maturation and reproductive functions. However, the relationship among NE, miR-7 and gonadotropin needs to be elucidated. The aim of this study was to identify whether miR-7 involved in the NE-adrenoceptor signaling pathway affects the synthesis and secretion of FSH and LH in porcine pituitary. Our results showed that the NE intracerebroventricular injection increased pituitary miR-7 level and the synthesis and secretion of FSH and LH in porcine, whereas the inhibition of either endogenous miR-7 or β-adrenergic receptors hindered the rise of FSH and LH synthesis induced by NE in cultured primary porcine anterior pituitary cells. Further, we identified the molecular type of β-adrenergic receptors and the signaling pathway in porcine pituitary, and we found that NE played its roles relying on adrenoceptor beta 2 (β2AR) and the RAF/MEK/ERK1/2 signaling pathway. The phosphorylation of ERK1/2 upregulated miR-7 level which subsequently enhanced FSH and LH synthesis by targeting to Golgi glycoprotein 1 (GLG1). These suggest that miR-7 mediates NE's effect on promoting FSH and LH synthesis in porcine pituitary.

摘要

微小 RNA-7(miR-7)是大量基因表达和相关生物过程的重要调节剂,在猪垂体中高度表达。去甲肾上腺素(NE)作为一种重要的神经递质或/和应激下过度分泌的激素,影响包括垂体促卵泡激素(FSH)和促黄体生成素(LH)在内的各种激素的合成和分泌,这些激素是调节性成熟和生殖功能的关键激素。然而,NE、miR-7 和促性腺激素之间的关系尚需阐明。本研究旨在确定 miR-7 是否参与 NE 肾上腺素能受体信号通路影响猪垂体中 FSH 和 LH 的合成和分泌。我们的结果表明,NE 脑室注射增加了猪垂体 miR-7 水平以及 FSH 和 LH 的合成和分泌,而内源性 miR-7 或β-肾上腺素受体的抑制作用阻碍了 NE 在培养的原代猪前垂体细胞中诱导的 FSH 和 LH 合成的增加。此外,我们鉴定了猪垂体中β-肾上腺素受体的分子类型和信号通路,发现 NE 依赖于肾上腺素能受体β2(β2AR)和 RAF/MEK/ERK1/2 信号通路发挥作用。ERK1/2 的磷酸化上调了 miR-7 水平,随后通过靶向高尔基糖蛋白 1(GLG1)增强了 FSH 和 LH 的合成。这些表明 miR-7 介导了 NE 促进猪垂体中 FSH 和 LH 合成的作用。

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