1α,25(OH)2D3改善小鼠颗粒细胞17β-雌二醇分泌，可能减轻内质网应激。

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-02-01 DOI:10.1016/j.bcp.2024.116696

Wenjing Lu, Xinjing Shi, Yuning Liu, Haolin Zhang, Zhengrong Yuan, Yingying Han, Qiang Weng

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引用次数: 0

摘要

维生素D3在女性生殖中起着重要的调节作用。然而，关于维生素D3与麝鼠繁殖之间关系的研究还很有限。本研究旨在确定活性形式维生素D3, 1α，25-二羟胺D3 [1α，25(OH)2D3]对麝鼠卵巢颗粒细胞（MGCs）的作用。结果表明，维生素D受体（VDR）明显定位于MGCs中，补充1α，25(OH)2D3增加了MGCs的VDR信号转导。同时，10 nM的1α，25(OH)2D3刺激MGCs分泌17β-雌二醇，增强了甾体生成酶mRNA的表达。1α,25(OH)2D3也通过表达GRP78、p-PERK、ATF4和CHOP显著下调MGCs内质网应激。此外，RNA-seq分析显示，10 nM的1α，25(OH)2D3激活了抑制MGCs凋亡的PI3K/Akt/mTOR和TNF通路。综上所述，这些发现表明，1α,25(OH) 2d3诱导的VDR信号可改善17β-雌二醇分泌，并可能通过PERK-ATF4-CHOP途径缓解MGCs内质网应激。

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1α,25(OH)2D3 improves 17β-estradiol secretion and potentially alleviates endoplasmic reticulum stress in muskrat granulosa cells

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1α,25(OH)2D3 improves 17β-estradiol secretion and potentially alleviates endoplasmic reticulum stress in muskrat granulosa cells

Vitamin D₃ plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D₃ and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D₃, 1α,25-dihydroxytamin D₃ [1α,25(OH)₂D₃], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)₂D₃ supplementation increased VDR signaling of MGCs. Meanwhile, 10 nM of 1α,25(OH)₂D₃ stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)₂D₃ also remarkably down-regulated MGCs endoplasmic reticulum stress according to the expression of GRP78, p-PERK, ATF4, and CHOP. In addition, RNA-seq analysis revealed that 10 nM of 1α,25(OH)₂D₃ activated the PI3K/Akt/mTOR and TNF pathways that contributed to the inhibition of MGCs apoptosis. Taken together, these findings suggest that 1α,25(OH)₂D₃-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.