The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells.
The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells.
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ERK1/2途径通过协调调节leydig细胞中类固醇基因的表达来调节睾丸激素的合成。
DOI：
10.1016/j.mce.2013.02.017
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发表时间：
2013-05-06
影响因子：
4.1
通讯作者：
Ascoli, Mario
中科院分区：
文献类型：
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作者：
Matzkin, Maria Eugenia;Yamashita, Soichi;Ascoli, Mario
间质细胞特异性缺失MAPK激酶1和2(mek1f/f；mek2−/−；Cre+)的成年小鼠表现为间质细胞发育不良和高促性腺激素减退症。我们利用放射免疫分析和定量聚合酶链式反应研究了参与胆固醇转化为睾酮的Leydig细胞基因(Star、Cyp11a1、Hsd3b6、CyP17a1和Hsd17b3)、雄激素代谢基因(Srda1和Dhrs9)以及调节类固醇生成基因表达的四个转录因子(Creb1、Nr5a1、Nr4a1和Nr0b1)的功能和表达。我们发现在成年Mek1f/f；Mek2−/−；Cre+小鼠的Ledyi细胞中，Star、Hsd3b6、CyP17a1和Hsd17b3表达下调，而srda1和Dhrs9表达上调，而Creb1、Nr5a1、Nr4a1和Nr0b1没有变化或上调。在功能上，所有下调的基因，而没有上调的基因，导致成年Mek1f/f；mek2−/−；Cre+小鼠睾丸间质细胞睾酮合成减少，因为它们在hCG刺激下或与睾酮前体如孕酮或雄烯二酮孵育时产生低睾酮和双氢睾酮。
Adult mice with a Leydig cell specific deletion of MAPK kinase (MEK) 1 and 2 (Mek1f/f;Mek2−/−;Cre+) mice display Leydig cell hypoplasia and hypergonadotropic hypogonadism. We used radioimmunoassays and quantitative PCR to evaluate the function and expression of the Leydig cell genes involved in the conversion of cholesterol to testosterone (Star, Cyp11a1, Hsd3b6, Cyp17a1 and Hsd17b3), androgen metabolism (Srda1 and Dhrs9), and four transcription factors (Creb1, Nr5a1, Nr4a1 and Nr0b1) that regulate the expression of steroidogenic genes. We show that Star, Hsd3b6, Cyp17a1 and Hsd17b3 are downregulated in Ledyig cells of adult Mek1f/f;Mek2−/−;Cre+ mice whereas Srda1 and Dhrs9 are upregulated and Creb1, Nr5a1, Nr4a1 and Nr0b1 are unchanged or upregulated. Functionally, all the downregulated genes but none of the upregulated genes contribute to the decrease in testosterone synthesis in Leydig cells of adult Mek1f/f;Mek2−/−;Cre+ mice because they produce low testosterone and dihydrotestosterone when stimulated with hCG or when incubated with testosterone precursors such as progesterone or androstenedione.
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影响因子：
4.1
作者：
Huhtaniemi, I;Rulli, S;Poutanen, M
通讯作者：
Poutanen, M
影响因子：
4.8
作者：
O'Shaughnessy, PJ;Baker, P;Huhtaniemi, I
通讯作者：
Huhtaniemi, I
影响因子：
4.1
作者：
Coonce MM;Rabideau AC;McGee S;Smith K;Narayan P
通讯作者：
Narayan P
影响因子：
4.8
作者：
Brion, Laura;Maloberti, Paula M.;Paz, Cristina
通讯作者：
Paz, Cristina
影响因子：
--
作者：
Lei, ZM;Mishra, S;Rao, CV
通讯作者：
Rao, CV