Second Clinical College, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Joint Program of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Mol Reprod Dev. 2019 Jun;86(6):714-726. doi: 10.1002/mrd.23149. Epub 2019 Apr 16.
Prolyl oligopeptidase (POP), one of the most widely distributed serine endopeptidases, is highly expressed in the ovaries. However, the physiological role of POP in the ovaries is not clear. In this study, we investigated the significance of POP in the corpus luteum. Murine luteal cells were cultured in vitro and treated with a POP selective inhibitor, (2S)-1[[(2 S)-1-(1-oxo-4-phenylbutyl)-2-pyrrolidinyl carbonyl]-2-pyrrolidinecarbonitrile (KYP-2047). We found that KYP-2047 treatment decreased progesterone secretion. In contrast, POP overexpression increased progesterone secretion. Three essential steroidogenic enzymes, including p450 cholesterol side-chain cleavage enzyme (CYP11A), 3β-hydroxysteroid dehydrogenase (3β-HSD), and the steroidogenic acute regulatory protein (StAR), were regulated by POP. Further studies showed that POP overexpression increased ERK1/2 phosphorylation and increased the expression of steroidogenic factor 1 (SF1), while KYP-2047 treatment decreased ERK1/2 phosphorylation and SF1 expression. To clarify the role of ERK1/2 signaling in POP-regulated progesterone synthesis, U0126-EtOH, an inhibitor of the ERK signaling pathway, was used to treat luteal cells. We found that U0126-EtOH decreased progesterone production and the expression of steroidogenic enzymes and SF1. POP overexpression did not reverse the effects of U0126-EtOH. Overall, POP regulates progesterone secretion by stimulating the expression of CYP11A, 3β-HSD, and StAR in luteal cells. ERK signaling and downstream SF1 expression contribute to this process.
脯氨酰寡肽酶（POP）是一种广泛分布的丝氨酸内肽酶，在卵巢中高度表达。然而，POP 在卵巢中的生理作用尚不清楚。在这项研究中，我们研究了 POP 在黄体中的意义。将鼠黄体细胞在体外培养并用 POP 选择性抑制剂（（2S）-1[[（2S）-1-（1-氧代-4-苯基丁基）-2-吡咯烷羰基]-2-吡咯烷甲腈（KYP-2047）处理。我们发现 KYP-2047 处理可降低孕激素分泌。相反，POP 过表达增加了孕激素分泌。三种必需的类固醇生成酶，包括 p450 胆固醇侧链裂解酶（CYP11A）、3β-羟甾脱氢酶（3β-HSD）和类固醇急性调节蛋白（StAR），受 POP 调节。进一步的研究表明，POP 过表达增加了 ERK1/2 的磷酸化并增加了类固醇生成因子 1（SF1）的表达，而 KYP-2047 处理则降低了 ERK1/2 的磷酸化和 SF1 的表达。为了阐明 ERK1/2 信号在 POP 调节孕激素合成中的作用，用 ERK 信号通路抑制剂 U0126-EtOH 处理黄体细胞。我们发现 U0126-EtOH 降低了孕激素的产生和类固醇生成酶和 SF1 的表达。POP 过表达并不能逆转 U0126-EtOH 的作用。总体而言，POP 通过刺激黄体细胞中 CYP11A、3β-HSD 和 StAR 的表达来调节孕激素的分泌。ERK 信号和下游的 SF1 表达有助于这一过程。
