Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Anatomy, School of medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cell Biochem Funct. 2018 Jun;36(4):183-193. doi: 10.1002/cbf.3330. Epub 2018 Apr 20.
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in reproductive-aged women. Hormonal abnormality caused by steroidogenesis disturbances appears to be the main culprit of the clinical picture in PCOS. Vitamin D3 could regulate steroidogenesis in granulosa cells, but the mechanism of action of vitamin D3 on steroidogenesis remains unknown. AMP-activated protein kinase (AMPK) has a modulating role in steroid hormone production. We investigated the effect of vitamin D3 on steroidogenesis in cultured granulosa cells of dehydroepiandrosterone-induced PCOS mice and studied the involvement of AMPK signalling pathway in the current process. Immunoblotting assay showed that vitamin D3 could increase phosphorylation of AMPK alpha and acetyl-CoA carboxylase, main substrate of AMPK. Vitamin D3 and 5-aminoimidazole-4-carboxamide-1-β-D-riboside or Aicar (AMPK activator) not only reduced gene expression of steroidogenic enzymes (P450scc or Cyp11a1, StAR, Cyp19a1 and 3B-HSD), but also reduced production of progesterone and 17B-estradiol assessed by radioimmunoassay. Pretreatment with compound C (AMPK inhibitor) decreased APMK phosphorylation and eliminated the effects of vitamin D3 and Aicar on steroidogenic enzymes expression and estradiol and progesterone production. This study showed that vitamin D3 has the main role in regulating of steroidogenesis in granulosa cells of mouse polycystic ovary through activation of the AMPK signalling pathway.
Polycystic ovarian syndrome (PCOS) is an endocrine disorder of women in reproductive age. This disorder is partly related to disruption in steroidogenesis pathway and dysregulation of estradiol and progesterone production in granulosa cells of polycystic ovaries. Previously, we have shown that vitamin D3 could modulate steroidogenesis pathway in PCOS granulosa cells. In this study, we investigate the molecular mechanism of vitamin D3 in regulation of steroidogenesis pathway. We have shown that vitamin D3 has a modulating role in steroidogenesis pathway of granulosa cells by regulation of AMP-activated protein kinase (AMPK) as an underlying molecular mechanism in mouse polycystic ovary.
多囊卵巢综合征（PCOS）是生殖期妇女的一种内分泌和代谢紊乱。类固醇生成障碍引起的激素异常似乎是 PCOS 临床特征的主要罪魁祸首。维生素 D3 可以调节颗粒细胞中的类固醇生成，但维生素 D3 对类固醇生成的作用机制尚不清楚。 AMP 激活的蛋白激酶（AMPK）在类固醇激素产生中具有调节作用。我们研究了维生素 D3 对脱氢表雄酮诱导的 PCOS 小鼠培养的颗粒细胞中类固醇生成的影响，并研究了 AMPK 信号通路在此过程中的参与情况。免疫印迹分析显示，维生素 D3 可以增加 AMPKα和乙酰辅酶 A 羧化酶的磷酸化，这是 AMPK 的主要底物。维生素 D3 和 5-氨基咪唑-4-甲酰胺-1-β-D-核糖苷或 Aicar（AMPK 激活剂）不仅降低了类固醇生成酶（P450scc 或 Cyp11a1、StAR、Cyp19a1 和 3B-HSD）的基因表达，还通过放射免疫分析降低了孕激素和 17β-雌二醇的产生。用化合物 C（AMPK 抑制剂）预处理可降低 AMPK 磷酸化，并消除维生素 D3 和 Aicar 对类固醇生成酶表达以及雌二醇和孕激素产生的影响。本研究表明，维生素 D3 通过激活 AMPK 信号通路在多囊卵巢小鼠颗粒细胞中起主要作用调节类固醇生成。
多囊卵巢综合征（PCOS）是生殖期妇女的一种内分泌紊乱。这种疾病部分与类固醇生成途径中断和多囊卵巢颗粒细胞中雌二醇和孕激素产生失调有关。此前，我们已经表明，维生素 D3 可以调节 PCOS 颗粒细胞中的类固醇生成途径。在这项研究中，我们研究了维生素 D3 调节类固醇生成途径的分子机制。我们已经表明，维生素 D3 通过调节 AMP 激活的蛋白激酶（AMPK）作为多囊卵巢小鼠中类固醇生成途径的潜在分子机制，在类固醇生成途径中发挥调节作用。
