Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
RBMCH Division, ICMR, New Delhi 110029, India.
J Steroid Biochem Mol Biol. 2024 Sep;242:106524. doi: 10.1016/j.jsbmb.2024.106524. Epub 2024 Apr 24.
The corpus luteum (CL) is a temporary endocrine gland that synthesizes progesterone. The luteal progesterone plays a central role in the regulation of the estrous cycle as well as the implantation and maintenance of pregnancy. Our previous study showed the expression of adropin and its receptor, GPR19, in the luteal cells and its significant role in luteinization. The aim of the present study was to investigate the in vitro effect of adropin on hCG-induced ovarian functions in adult mice. We also evaluated the effect of exogenous treatment with adropin on ovarian steroidogenesis and anti-oxidant parameters, with special emphasis on CL function. Our results demonstrated that adropin acts synergistically with hCG to promote ovarian steroidogenesis and survival by increasing the expression of StAR, 3β-HSD, and aromatase proteins and decreasing the BAX/BCL2 ratio. Exogenous adropin treatment increased progesterone production by increasing the expression of GPR19, StAR and 3β-HSD enzymes in the mouse ovary. Also, adropin inhibited the luteal oxidative stress by increasing nuclear translocation of NRF-2 in CL, which resulted in increased HO-1 expression and SOD, catalase activity. Decreased oxidative stress might inhibit the translocation of NF-κB into the nucleus of luteal cells, resulting into increased survival and decreased apoptosis, as evident by decreased lipid peroxidation, BAX/BCL2 ratio, caspase 3, active caspase 3 expression, and TUNEL-positive cells in adropin treated mice. Our findings suggest that adropin can be a promising candidate that can enhance the survivability of the CL.
黄体(CL)是一种临时内分泌腺,合成孕激素。黄体孕激素在调节发情周期以及胚胎着床和维持妊娠中起着核心作用。我们之前的研究表明,ADROPIN 及其受体 GPR19 在黄体细胞中的表达及其在黄体化中的重要作用。本研究旨在探讨 ADROPIN 对成年小鼠 hCG 诱导的卵巢功能的体外作用。我们还评估了外源性 ADROPIN 处理对卵巢甾体生成和抗氧化参数的影响,特别强调 CL 功能。我们的结果表明,ADROPIN 与 hCG 协同作用,通过增加 StAR、3β-HSD 和芳香酶蛋白的表达,降低 BAX/BCL2 比值,促进卵巢甾体生成和存活。外源性 ADROPIN 处理通过增加 GPR19、StAR 和 3β-HSD 酶在小鼠卵巢中的表达来增加孕激素的产生。此外,ADROPIN 通过增加 CL 中 NRF-2 的核易位来抑制黄体氧化应激,导致 HO-1 表达和 SOD、过氧化氢酶活性增加。氧化应激的减少可能会抑制 NF-κB 向黄体细胞核内的易位,导致细胞存活增加和凋亡减少,这表现在 ADROPIN 处理的小鼠中脂质过氧化、BAX/BCL2 比值、caspase 3、活性 caspase 3 表达和 TUNEL 阳性细胞减少。我们的研究结果表明,ADROPIN 可能是一种有前途的候选药物,可以增强 CL 的存活能力。