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雌性膜联蛋白A5基因敲除小鼠垂体中基因表达的增强与抑制

Augmentation of and Suppression of Expression in the Pituitary Gland of Female Annexin A5 Null Mouse.

作者信息

Terashima Ryota, Saigo Tomotaka, Laoharatchatathanin Titaree, Kurusu Shiro, Brachvogel Bent, Pöschl Ernst, Kawaminami Mitsumori

机构信息

Laboratory of Veterinary Physiology, School of Veterinary Medicine, Kitasato University, Aomori, Japan.

Clinic for Small Domestic Animals and Radiology, Faculty of Veterinary Medicine, Mahanakorn University of Technology, Bangkok, Thailand.

出版信息

J Endocr Soc. 2020 Jul 16;4(9):bvaa096. doi: 10.1210/jendso/bvaa096. eCollection 2020 Sep 1.

Abstract

GnRH enhances the expression of annexin A5 (ANXA5) in pituitary gonadotropes, and ANXA5 enhances gonadotropin secretion. However, the impact of ANXA5 regulation on the expression of pituitary hormone genes remains unclear. Here, using quantitative PCR, we demonstrated that ANXA5 deficiency in female mice reduced the expression of and in their pituitary glands. Transcriptome analysis confirmed a specific increase in mRNA expression in addition to lower levels of expression in ANXA5-deficient female pituitary glands. This gene was then found to be a GnRH-inducible immediate early gene, and its increased expression caused protein to accumulate in the nucleus after administration of a GnRH agonist in LβT2 cells, which are an in vitro pituitary gonadotrope model. The increase in ANXA5 protein levels in LβT2 cells clearly suppressed expression. siRNA-mediated inhibition of expression increased expression. The results revealed that GnRH stimulates and sequentially. NR4A3 suppression of may be necessary for later massive secretion of FSH by GnRH in gonadotropes, and would be negatively regulated by ANXA5 to increase FSH secretion.

摘要

促性腺激素释放激素(GnRH)可增强垂体促性腺细胞中膜联蛋白A5(ANXA5)的表达,而ANXA5可促进促性腺激素的分泌。然而,ANXA5调控对垂体激素基因表达的影响仍不清楚。在此,我们通过定量PCR证明,雌性小鼠中ANXA5的缺乏会降低其垂体中[具体基因1]和[具体基因2]的表达。转录组分析证实,除了ANXA5缺陷雌性垂体中[具体基因3]表达水平较低外,[具体基因4]的mRNA表达有特异性增加。随后发现该基因是一种GnRH诱导的即时早期基因,在体外垂体促性腺细胞模型LβT2细胞中给予GnRH激动剂后,其表达增加导致蛋白质在细胞核中积累。LβT2细胞中ANXA5蛋白水平的增加明显抑制了[具体基因5]的表达。小干扰RNA(siRNA)介导的[具体基因5]表达抑制增加了[具体基因6]的表达。结果表明,GnRH依次刺激[具体基因5]和[具体基因6]。NR4A3对[具体基因5]的抑制可能是GnRH随后在促性腺细胞中大量分泌促卵泡激素(FSH)所必需的,而[具体基因6]会受到ANXA5的负调控以增加FSH分泌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f93/7448937/7cbc8d1486c8/bvaa096f0001.jpg

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