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