Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells
Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells
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脯氨酰寡肽酶通过 ERK 信号通路调节小鼠黄体细胞中的孕酮分泌
DOI：
10.1002/mrd.23149
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发表时间：
2019-06
影响因子：
2.5
通讯作者：
Zhang Chunping
中科院分区：
文献类型：
--
作者：
Xu Ping;Bao Riqiang;Zhang Yaqiong;Lu Enhang;Feng Fen;Zhang Luyin;Li Jiaheng;Wang Jing;Tan Ximin;Tang Min;Hu Chuan;Li Gang;Zhang Chunping
脯氨酰寡肽酶（POP）是分布最广的丝氨酸内肽酶之一，在卵巢中高表达。然而，POP在卵巢中的生理作用尚不清楚。在这项研究中，我们探讨了POP在黄体中的意义。体外培养小鼠黄体细胞，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-吡咯烷腈（KYP-2047）处理。我们发现KYP-2047处理降低了孕酮分泌。相反，POP过表达增加孕酮分泌。三种必需的类固醇生成酶，包括p450胆固醇侧链裂解酶（CYP 11 A）、3β-羟基类固醇脱氢酶（3β-HSD）和类固醇生成急性调节蛋白（星星），受POP调节。进一步的研究表明POP过表达增加ERK 1/2磷酸化和增加类固醇生成因子1（SF 1）的表达，而KYP-2047处理降低ERK 1/2磷酸化和SF 1表达。为了阐明ERK 1/2信号传导在POP调节的孕酮合成中的作用，使用ERK信号传导途径的抑制剂U 0126-EtOH处理黄体细胞。我们发现，U 0126-EtOH降低了孕酮的产生以及类固醇生成酶和SF 1的表达。POP过表达没有逆转U 0126-EtOH的作用。总体而言，POP通过刺激黄体细胞中CYP 11 A、3β-HSD和星星的表达来调节孕酮分泌。ERK信号传导和下游SF 1表达有助于这一过程。
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.
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影响因子：
4.8
作者：
Dewi, DA;Abayasekara, DRE;Wheeler-Jones, CPD
通讯作者：
Wheeler-Jones, CPD
影响因子：
4.1
作者：
Sahmi, M;Nicola, ES;Price, CA
通讯作者：
Price, CA
影响因子：
--
作者：
S. Kyosseva
通讯作者：
S. Kyosseva
影响因子：
3.2
作者：
Myohanen, Timo T.;Pyykko, Elisa;Carpen, Olli
通讯作者：
Carpen, Olli
影响因子：
2.5
作者：
A. Kimura;J. Ohnishi;Hikari Okimura;T. Hamabata;Takayuki Takahashi
通讯作者：
A. Kimura;J. Ohnishi;Hikari Okimura;T. Hamabata;Takayuki Takahashi