TGFB1 represses the expression of SF1 and LRH1 to inhibit E2 production in rat LCs.
TGFB1 represses the expression of SF1 and LRH1 to inhibit E2 production in rat LCs.
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TGFB1 抑制 SF1 和 LRH1 的表达，从而抑制大鼠 LC 中 E2 的产生。
DOI：
10.1530/rep-16-0044
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发表时间：
2017-05
期刊：
影响因子：
3.8
通讯作者：
Li Zhen
中科院分区：
文献类型：
--
作者：
Yang Qianqian;Ma Binfang;Qiao Huilian;Ma He;Dong Yuhang;Cao Liang;Ma Jing;Li Zhen
成年睾丸中的间质细胞是雌激素产生的主要场所，对哺乳动物生殖细胞的分化至关重要。我们以前的工作表明，转化生长因子β1(TGFB1)通过下调Cyp19基因的表达来抑制成熟大鼠LCS雌二醇(E_2)的分泌。然而，其机制仍不清楚。本研究观察了TGFB1对原代培养LCs和大鼠睾丸中类固醇生成因子1(SF1)、肝脏受体同系物1(LRH1)、cAMP反应元件结合蛋白(CREB)和cAMP反应元件调节剂(CREM)表达水平的影响。然后应用TGFb 1型受体(TGFBR1)抑制剂SB431542验证TGFB1信号参与SF1和LRH1表达的调节。检测睾丸LCS中细胞色素P19的表达，并测定睾丸间质液(TIF)中雌二醇(E2)的含量。结果表明，TGFB1对原代培养的LCs和大鼠睾丸中SF1和LRH1的表达水平均有明显的下调作用。体内实验还观察到TGFB1对TIF分泌E2和睾丸LCS中细胞色素P19表达的下调作用，这种抑制作用可被TGFBR1抑制剂SB431542逆转。我们的发现表明，TGFB1可能通过涉及Alk5的典型信号通路来抑制SF1和LRH1的积聚，最终抑制LCS中Cyp19的转录和雌激素的产生。
Leydig cells (LCs) in the adult testis have been identified as the major sites of oestrogen production, which is crucial for mammalian germ cell differentiation. Our previous work showed that transforming growth factor beta 1 (TGFB1) inhibits estradiol (E2) secretion via down-regulating Cyp19 gene expression in mature rat LCs. However, the mechanism remains unclear. In the present study, the effects of TGFB1 on the expression levels of steroidogenic factor 1 (SF1), liver receptor homolog 1 (LRH1), cAMP response element-binding protein (CREB) and cAMP responsive element modulator (CREM) were evaluated both in primary cultured LCs and in rat testis. The involvement of TGFB1 signalling in the regulation of SF1 and LRH1 expression was then validated by applying the inhibitor of the TGFB type 1 receptor (TGFBR1) SB431542. Moreover, the expression of CYP19 in testicular LCs was investigated and the production of E2 in testicular interstitial fluid (TIF) was measured. The results showed that TGFB1 especially down-regulated the expression levels of SF1 and LRH1 both in primary cultured LCs and in rat testis. The down-regulations of TGFB1 in the production of E2 in TIF and the expression of CYP19 in testicular LCs were also observed in vivo These inhibitory effects could be reversed by TGFBR1 inhibitor SB431542. Our findings suggest that TGFB1 may act through the canonical signalling pathway involving ALK5 to restrain SF1 and LRH1 accumulation and eventually attenuate Cyp19 transcription and oestrogen production in LCs.
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影响因子：
3.8
作者：
Haakensen VD;Bjøro T;Lüders T;Riis M;Bukholm IK;Kristensen VN;Troester MA;Homen MM;Ursin G;Børresen-Dale AL;Helland Å
通讯作者：
Helland Å
影响因子：
1.6
作者：
Cg Özgüden-Akkoç;A. Özer
通讯作者：
Cg Özgüden-Akkoç;A. Özer
影响因子：
2.1
作者：
Candela R González;R. Calandra;S. González-Calvar
通讯作者：
Candela R González;R. Calandra;S. González-Calvar
影响因子：
2.1
作者：
S. Carreau;S. Bourguiba;S. Lambard;D. Silandre;C. Delalande
通讯作者：
S. Carreau;S. Bourguiba;S. Lambard;D. Silandre;C. Delalande
影响因子：
3.8
作者：
C. Itman;S. Mendis;B. Barakat;K. Loveland
通讯作者：
C. Itman;S. Mendis;B. Barakat;K. Loveland