Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
Clinical Research Centre, National Centre of Translational and Clinical Research, University of Tartu, Ravila 19, 50411 Tartu, Estonia.
Int J Mol Sci. 2019 Jun 23;20(12):3068. doi: 10.3390/ijms20123068.
The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor primarily known for its toxicological functions. Recent studies have established its importance in many physiological processes including female reproduction, although there is limited data about the precise mechanisms how Ahr itself is regulated during ovarian follicle maturation. This study describes the expression of Ahr in ovarian granulosa cells (GCs) of immature mice in a gonadotropin-dependent manner. We show that Ahr upregulation in vivo requires both follicle stimulating hormone (FSH) and luteinizing hormone (LH) activities. FSH alone increased mRNA, but had no effect on Ahr protein level, implicating a possible LH-dependent post-transcriptional regulation. Also, the increase in Ahr protein is specific to large antral follicles in induced follicle maturation. We show that expression in GCs of mid-phase follicular maturation is downregulated by protein kinase A (PKA) signaling and activation of promoter is regulated by chromatin remodeling.
芳香烃受体（Ahr）是一种配体激活的转录因子，主要因其毒理学功能而为人所知。最近的研究表明，它在许多生理过程中都很重要，包括女性生殖，尽管关于 Ahr 本身在卵巢卵泡成熟过程中是如何被精确调控的，相关数据仍十分有限。本研究描述了芳香烃受体在未成熟小鼠卵巢颗粒细胞（GCs）中的表达情况，该表达是依赖促性腺激素的。我们发现体内 Ahr 的上调需要卵泡刺激素（FSH）和黄体生成素（LH）的共同作用。FSH 单独增加了 mRNA，但对 Ahr 蛋白水平没有影响，暗示可能存在 LH 依赖的转录后调控。此外，Ahr 蛋白的增加是诱导卵泡成熟中大型窦卵泡特有的。我们表明，在中期卵泡成熟的 GC 中， 表达被蛋白激酶 A（PKA）信号下调， 启动子的激活受到染色质重塑的调控。
