Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Reproduction. 2024 Sep 26;168(5). doi: 10.1530/REP-24-0240. Print 2024 Nov 1.
Cordycepin (COR), a compound derived from Cordyceps, is recognized as an adenosine analog with numerous beneficial effects on human health. However, its impact on steroidogenic acute regulatory protein (STAR) expression in ovarian granulosa cells is not well understood. This study demonstrates that COR downregulates STAR expression by reducing the expression of the SP1 transcription factor.
Cordycepin (COR), a pure compound of Cordyceps, is known as an adenosine analog that exerts many beneficial effects on human health. The steroidogenesis mediated by ovarian granulosa cells is pivotal in maintaining normal female reproductive function. The steroidogenic acute regulatory protein (STAR) regulates the rate-limiting step in steroidogenesis. COR has been shown to stimulate STAR expression in mouse Leydig cells, the steroidogenic cells in the testes. However, the effect of COR on STAR expression in ovarian granulosa cells remains undetermined. In the present study, we show that treatment with COR downregulates STAR expression in a steroidogenic human granulosa-like tumor cell line, KGN, and primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing in vitro fertilization. We used specific adenosine receptor (AR) antagonists, and our results reveal that the inhibitory effect of COR on STAR expression is mediated by AR-A1, AR-A2A, and AR-A3. In both KGN and primary hGL cells, COR activates ERK1/2 and AKT signaling pathways, but only activation of ERK1/2 is required for the COR-induced downregulation of STAR expression. In addition, our results demonstrate that COR downregulates STAR expression by reducing the expression of the SP1 transcription factor. These results provide a better understanding of the biological function of COR on STAR expression in the ovary, which may lead to the development of alternative therapeutic approaches for female reproductive disorders.
蛹虫草素（COR）是一种从蛹虫草中提取的化合物，被认为是一种腺苷类似物，对人类健康有许多有益的影响。然而，其对卵巢颗粒细胞中类固醇生成急性调节蛋白（STAR）表达的影响尚不清楚。本研究表明，COR 通过降低 SP1 转录因子的表达来下调 STAR 表达。
蛹虫草素（COR）是蛹虫草的纯化合物，被称为腺苷类似物，对人类健康有许多有益的影响。卵巢颗粒细胞介导的甾体生成对于维持正常的女性生殖功能至关重要。类固醇生成急性调节蛋白（STAR）调节甾体生成中的限速步骤。COR 已被证明可刺激睾丸中甾体生成细胞——老鼠 Leydig 细胞中的 STAR 表达。然而，COR 对卵巢颗粒细胞中 STAR 表达的影响尚不确定。在本研究中，我们表明 COR 处理可下调类固醇生成人颗粒状细胞瘤系 KGN 和从接受体外受精的患者中获得的人颗粒细胞-黄体（hGL）细胞的原代培养物中的 STAR 表达。我们使用了特定的腺苷受体（AR）拮抗剂，结果表明 COR 对 STAR 表达的抑制作用是通过 AR-A1、AR-A2A 和 AR-A3 介导的。在 KGN 和原代 hGL 细胞中，COR 激活 ERK1/2 和 AKT 信号通路，但仅 ERK1/2 的激活是 COR 诱导的 STAR 表达下调所必需的。此外，我们的结果表明 COR 通过降低 SP1 转录因子的表达来下调 STAR 表达。这些结果提供了对 COR 在卵巢中对 STAR 表达的生物学功能的更好理解，这可能为女性生殖障碍的治疗方法的开发提供新的思路。
