虫草素 (COR) 是虫草的纯化合物，被称为腺苷类似物，对人类健康产生许多有益的影响。卵巢颗粒细胞介导的类固醇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）调节类固醇生成的限速步骤。 COR 已被证明可以刺激小鼠 Leydig 细胞（睾丸中的类固醇生成细胞）中 StAR 的表达。然而，COR 对卵巢颗粒细胞 StAR 表达的影响仍未确定。在本研究中，我们表明，COR 治疗可下调类固醇生成人颗粒样肿瘤细胞系 KGN 以及从接受体外受精的患者获得的人颗粒叶黄素 (hGL) 细胞的原代培养物中 StAR 的表达。使用特定的腺苷受体 (AR) 拮抗剂，我们的结果表明 COR 对 StAR 表达的抑制作用是由 AR-A1、-A2A 和 -A3 介导的。在 KGN 和原代 hGL 细胞中，COR 都会激活 ERK1/2 和 AKT 信号通路，但 COR 诱导的 StAR 表达下调只需要激活 ERK1/2。此外，我们的结果表明，COR 通过减少 SP1 转录因子的表达来下调 StAR 表达。这些结果使人们更好地了解 COR 对卵巢中 StAR 表达的生物学功能，这可能会导致女性生殖疾病替代治疗方法的开发。

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. Using specific adenosine receptor (AR) antagonists, our results reveal that the inhibitory effect of COR on StAR expression is mediated by AR-A1, -A2A, and -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.