Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells
Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells
复制标题
DOI：
10.1677/jme-07-0076
复制
发表时间：
2007-11-01
影响因子：
3.5
通讯作者：
Yanase, Toshihiko
中科院分区：
文献类型：
--
作者：
Tanaka, Tomoko;Gondo, Shigeki;Yanase, Toshihiko
类固醇生成因子1/肾上腺4结合蛋白（SF-1/Ad 4 BP）是类固醇生成以及肾上腺和性腺发育所必需的核受体。骨髓间充质细胞（BMCs）含有多能祖细胞COS，可分化为多个谱系。在以前的研究中，我们报道了腺病毒介导的SF-1的强制表达可以将小鼠原代长期培养的BMCs转化为类固醇生成细胞。对于未来的临床应用，使用人BMCs的试验将是必不可少的。在这项研究中，我们研究了SF-1是否可以将人BMCs转化为类固醇生成细胞，并比较了这些细胞与小鼠类固醇生成BMCs的类固醇特征。原代培养的人BMCs感染含牛SF-1 cDNA的腺病毒后可产生孕酮、皮质酮、皮质醇、脱氢表雄酮、睾酮和雌二醇。人骨髓细胞中肾上腺和性腺类固醇产生的这种混合特征得到了P450 SCC、3 β-羟基类固醇脱氢酶（3 p-HSD）、P450 c21、P450 c11、P450 c17、17 β-HSD和P450 arom mRNA表达的支持。与小鼠类固醇生成BMC不同，SF-1引入人BMC引起ACTH和LH受体的显著诱导，从而分别导致细胞对ACTH和LH的良好反应性。重要的是，在已知与肾上腺和/或性腺发育密切相关的几个因子中，仅引入SF-1使人BMC能够表达P450 SCC并产生皮质醇和睾酮，这表明SF-1确实是从人BMC产生类固醇生成细胞的主要调节剂。
Steroidogenic factor 1/adrenal 4 binding protein (SF-1/Ad4BP) is an essential nuclear receptor for steroidogenesis as well as for adrenal and gonadal gland development. Mesenchymal bone marrow cells (BMCs) contain pluripotent progenitor COS, which differentiate into multiple lineages. In a previous study, we reported that adenovirus-mediated forced expression of SF-1 could transform mouse primary long-term cultured BMCs into steroidogenic cells. For future clinical application, trials using human BMCs would be indispensable. In this study, we examined whether SF-1 could transform human BMCs into steroidogenic cells and compared the steroid profile of these cellswith that of mouse steroidogenic BMCs. Primary cultured human BMCs infected with adenovirus containing bovine SF-1 cDNA could produce progesterone, corticosterone, cortisol, clehydroepiandrosterone, testosterone, and estradiol. Such a mixed character of adrenal and gonadal steroid production in human BMCs was supported by the expressions of P450scc, 3 beta-hydroxysteroid dehydrogenase (3p-HSD), P450c21, P450c11, P450c17, 17 beta-HSD, and P450arom mRNAs. Unlike mouse steroidogenic BMCs, introduction of SF-1 into human BMCs caused dramatic inductions of both ACTH and LH receptors, thus leading to good responsiveness of the cells to ACTH and LH respectively. Importantly, among several factors that are known to be closely associated with adrenal and/or gonadal development, introduction of only SF-1 enabled the human BMCs to express P450scc and to produce cortisol and testosterone, suggesting that SF-1 is truly a master regulator for the production of steroidogenic cells from human BMCs.