Deficiency of Gpr1 improves steroid hormone abnormality in hyperandrogenized mice.
Deficiency of Gpr1 improves steroid hormone abnormality in hyperandrogenized mice.
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Gpr1 缺乏可改善雄激素过多小鼠的类固醇激素异常
DOI：
10.1186/s12958-018-0363-9
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发表时间：
2018-05-24
期刊：
影响因子：
--
通讯作者：
Zhang JV
中科院分区：
文献类型：
--
作者：
Yang YL;Sun LF;Yu Y;Xiao TX;Wang BB;Ren PG;Tang HR;Zhang JV
背景：多囊卵巢综合征（PCOS）是一种具有多种表型的复杂遗传性疾病。许多研究使用脱氢表雄酮（DHEA）诱导青春期小鼠PCOS模型。本研究的目的是探讨GPR 1在脱氢表雄酮（DHEA）诱导的高雄激素化小鼠中的作用。方法：青春期前C57 BL/6小鼠（25日龄）和GPR 1缺陷小鼠均分为两组，每天注射芝麻油（含或不含DHEA）（6 mg/100 g），连续21天。进行苏木精和伊红（H&E）染色以确定DHEA处理的卵巢的特征。实时荧光定量PCR检测类固醇合成酶基因表达。结果：DHEA处理可诱导野生型小鼠PCOS的某些方面，如体重增加，血清睾酮水平升高，小卵泡、囊状卵泡、闭锁卵泡数量增加，卵巢中黄体缺失。然而，GPR 1缺陷显着衰减DHEA诱导的体重增加和卵巢表型，提高卵巢类固醇合成和培养的颗粒细胞中的雌二醇合成，部分通过mTOR signaling.Conclusions：总之，GPR 1缺陷导致改善类固醇合成的小鼠hyperandrogenized与DHEA，表明GPR 1可能是DHEA诱导的高雄激素血症的治疗靶点。
Background:Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice.Methods:Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real-time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1-mediated estradiol secretion.Results:DHEA treatment induced some aspects of PCOS in wild-type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling.Conclusions:In conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism.
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影响因子：
4.4
作者：
Barber, Thomas M.;Dimitriadis, George K.;Franks, Stephen
通讯作者：
Franks, Stephen
DOI：
10.1016/j.cbpb.2009.12.005
发表时间：
2010-04-01
影响因子：
2.2
作者：
Chen, Juan;Tang, Xue;Zou, Sixiang
通讯作者：
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影响因子：
38.9
作者：
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通讯作者：
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影响因子：
5.8
作者：
MORISHIMA, A;GRUMBACH, MM;QIN, K
通讯作者：
QIN, K
影响因子：
4.4
作者：
Chapman, John C.;Min, Soo Hong;Michael, Sandra D.
通讯作者：
Michael, Sandra D.