Merhi Zaher
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Mol Cell Endocrinol. 2019 Jan 5;479:87-92. doi: 10.1016/j.mce.2018.09.004. Epub 2018 Sep 22.
Vitamin D3 (1,25-dihydroxyvitamin D3, VD3) in vitro attenuates the effect of the pro-inflammatory advanced glycation end products (AGEs) on steroidogenesis in human granulosa cells (GCs) by downregulating the receptor for AGEs (RAGE). It has been shown that VD3 alone downregulates anti-Mullerian hormone (AMH) type 2 receptor (AMHR-2) gene expression and suppresses AMH-induced SMAD 1/5/8 phosphorylation in granulosa cells. However, the effect of AGEs, in the absence or presence of VD3, on AMH action in GCs has not been studied. Using human GCs, this study showed that human glycated albumin (HGA), an in vitro representative for AGEs, upregulated AMHR-2 mRNA but did not alter AMH mRNA expression levels. VD3 inhibited the HGA-induced increase in AMHR-2 mRNA expression levels. In KGN granulosa cell line, recombinant AMH induced SMAD 1/5/8 phosphorylation. HGA augmented the recombinant AMH-induced SMAD 1/5/8 phosphorylation while the addition of VD3 to HGA attenuated the recombinant AMH-induced SMAD 1/5/8 phosphorylation. Thus, AGEs could potentially affect folliculogenesis as reflected by changes in AMH signaling. These findings have significant implications for women with polycystic ovary syndrome who have significantly elevated serum and ovarian AGEs.
维生素D3（1,25 - 二羟基维生素D3，VD3）在体外通过下调晚期糖基化终产物（AGEs）受体（RAGE），减弱促炎的AGEs对人颗粒细胞（GCs）类固醇生成的影响。研究表明，单独的VD3会下调颗粒细胞中抗苗勒管激素（AMH）2型受体（AMHR - 2）的基因表达，并抑制AMH诱导的颗粒细胞中SMAD 1/5/8磷酸化。然而，在不存在或存在VD3的情况下，AGEs对GCs中AMH作用的影响尚未得到研究。本研究使用人GCs表明，AGEs的体外代表物人糖化白蛋白（HGA）上调了AMHR - 2 mRNA，但未改变AMH mRNA表达水平。VD3抑制了HGA诱导的AMHR - 2 mRNA表达水平的增加。在KGN颗粒细胞系中，重组AMH诱导了SMAD 1/5/8磷酸化。HGA增强了重组AMH诱导的SMAD 1/5/8磷酸化，而在HGA中添加VD3则减弱了重组AMH诱导的SMAD 1/5/8磷酸化。因此，AGEs可能会通过AMH信号通路的变化潜在地影响卵泡发生。这些发现对多囊卵巢综合征患者具有重要意义，这类患者血清和卵巢中的AGEs显著升高。
