The promoter(s) of the aromatase gene in male testicular cells.
The promoter(s) of the aromatase gene in male testicular cells.
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DOI：
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发表时间：
2004-03
影响因子：
2.1
通讯作者：
S. Carreau;S. Bourguiba;S. Lambard;D. Silandre;C. Delalande
中科院分区：
文献类型：
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作者：
S. Carreau;S. Bourguiba;S. Lambard;D. Silandre;C. Delalande
芳香化酶是哺乳动物雌激素生物合成的终端酶；它存在于包括生殖细胞在内的各种睾丸细胞中。芳香酶基因（Cyp19）在人类中是独特的，其表达在组织中受到调节，更准确地说，通过位于第一外显子的各种启动子的替代使用，以细胞特异性的方式进行调节。然而，关于睾丸芳香化酶尤其是生殖细胞中芳香化酶的调控的信息很少。这促使我们研究Cyp19基因表达的控制及其在睾丸雄激素/雌激素比调节中的作用。促性腺激素和cAMP调节体细胞中芳香酶的表达，证实启动子II是通过CRE控制的。此外，我们已经证明，在来自成年大鼠的高度纯化的生殖细胞（粗线精细胞和圆形精细胞）中，转化生长因子β (tgfβ)抑制了两种生殖细胞类型中Cyp19的表达。相反，肿瘤坏死因子α (TNFalpha)刺激粗筋素精母细胞中Cyp19的表达。地塞米松存在时，TNFalpha的作用被放大。因此，我们认为在生殖细胞中，TNF α通过粗线型精母细胞中的启动子PI.4增强芳香化酶的表达，可能是通过GAS元件上游的AP1位点，而在圆形精母细胞中，TNF需要糖皮质激素作为共刺激剂来增加Cyp19基因的表达。此外，我们已经证明雄激素和雌激素本身可以调节Cyp19基因在所有睾丸细胞类型中的表达，这表明ARE和ERE存在于Cyp19基因启动子上。最后，当存在精管或支持细胞条件培养基时，间质细胞和生殖细胞中的芳香化酶转录物增加，这表明其他局部产生的调节剂（如LRH-1）参与了芳香化酶基因表达的调节，特别是在间质细胞中。利用RACE (fast Amplification of cDNA Ends)-PCR，我们证实启动子II主要指导芳香化酶基因在大鼠睾丸细胞类型中的表达。然而，也建议另一个启动子如PI.4的参与。
Aromatase is the terminal enzyme responsible for estrogen biosynthesis in mammals; it is present in various testicular cells including germ cells. The aromatase gene (Cyp19) is unique in humans and its expression is regulated in a tissue and more precisely, in a cell-specific manner via the alternative use of various promoters located in the first exon. Nevertheless, there is little information concerning the regulation of the testicular aromatase especially in germ cells. This prompted us to study the control of Cyp19 gene expression and its role in the regulation of the testicular androgen/estrogen ratio. Gonadotrophins and cAMP modulate aromatase expression in somatic cells which confirms that promoter II is controlled via CRE. Moreover, we have demonstrated that in highly purified germ cells from adult rats (pachytene spermatocytes and round spermatids), transforming growth factor beta (TGFbeta) inhibited the expression of Cyp19 in both germ cell types. In contrast, tumor necrosis factor alpha (TNFalpha) stimulated Cyp19 expression in pachytene spermatocytes. The effect of TNFalpha is amplified in presence of dexamethasone. Therefore, we suggest that in germ cells, TNFalpha enhances expression of aromatase through promoter PI.4 in pachytene spermatocytes, possibly via an AP1 site upstream the GAS element, while in round spermatids TNF requires glucocorticoids as a co-stimulator to increase Cyp19 gene expression. In addition, we have shown that androgens and estrogens by themselves modulate Cyp19 gene expression in all testicular cell types studied suggesting the presence of ARE and ERE on the Cyp19 gene promoter(s). Finally, in presence of seminiferous tubules or Sertoli cell-conditioned media, aromatase transcripts are increased in both Leydig cells and germ cells suggesting that other locally produced modulators (e.g. LRH-1) are involved in the regulation of the aromatase gene expression especially in Leydig cells. Using RACE (Rapid Amplification of cDNA Ends)-PCR, we have confirmed that promoter II mainly directs expression of the aromatase gene in all testicular cell types studied in the rat. However, involvement of another promoter such as PI.4 is suggested as well.