Developmental and hormonal regulation of murine scavenger receptor, class B, type 1
Developmental and hormonal regulation of murine scavenger receptor, class B, type 1
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DOI：
10.1210/me.13.9.1460
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发表时间：
1999-09-01
影响因子：
--
通讯作者：
Hobbs, HH
中科院分区：
文献类型：
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作者：
Cao, GQ;Zhao, LP;Hobbs, HH
清道夫受体，B类，I型(SR-BI)，是啮齿类动物体内向类固醇生成组织供应血浆胆固醇的主要受体。我们以前已经证明类固醇生成因子-1(SF-1)与人SR-BI启动子中的一个序列结合，该序列的完整性是在培养的肾上腺皮质肿瘤细胞中高水平表达SR-BI所必需的。我们现在提供了SF-1调节SR-BI的体内证据。在小鼠胚胎发育过程中，SR-BI mRNA最初在两性生殖器脊中表达，并持续存在于发育中的睾丸，而不是卵巢。SR-BI在性腺中表达的这种性别二态表达图谱反映了SF-1的表达。在第11.5d的SF-1基因敲除胚胎的性腺脊部未检测到SR-BI基因。SR-BI和SF-1mRNA在新生肾上腺皮质细胞均有表达。这些研究直接支持SF-1参与体内SR-BI的调节。我们观察了cAMP对小鼠肾上腺皮质细胞(Y1-BS1)和睾丸癌细胞间质细胞(MA-10)SR-BI基因和蛋白表达的影响。诱导的时间进程与cAMP和SF-1调节的其他基因的时间进程惊人地相似。添加脂蛋白降低了Y1-BS1细胞中SR-BI的表达，这种作用被cAMP类似物逆转。在缺乏激素性急性调节蛋白的基因敲除小鼠的肾上腺中，SR-BI的mRNA和蛋白高水平表达；这些小鼠的肾上腺皮质细胞中有广泛的脂肪沉积，循环中ACTH水平较高。综上所述，这些研究表明，营养激素可以推翻胆固醇对SR-BI表达的抑制作用，从而确保类固醇的合成在应激期间保持不变。
The scavenger receptor, class B, type I (SR-BI), is the predominant receptor that supplies plasma cholesterol to steroidogenic tissues in rodents. We showed previously that steroidogenic factor-1 (SF-1) binds a sequence in the human SR-BI promoter whose integrity is required for high-level SR-BI expression in cultured adrenocortical tumor cells. We now provide in vivo evidence that SF-1 regulates SR-BI. During mouse embryogenesis, SR-BI mRNA was initially expressed in the genital ridge of both sexes and persisted in the developing testes but not ovary. This sexually dimorphic expression profile of SR-BI expression in the gonads mirrors that of SF-1. No SR-BI mRNA was detected in the gonadal ridge of day 11.5 SF-1 knockout embryos. Both SR-BI and SF-1 mRNA were expressed in the cortical cells of the nascent adrenal glands. These studies directly support SF-1 participating in the regulation of SR-BI in vivo. We examined the effect of cAMP on SR-BI mRNA and protein in mouse adrenocortical (Y1-BS1) and testicular carcinoma Leydig (MA-10) cells. The time courses of induction were strikingly similar to those described for other cAMP- and SF-1-regulated genes. Addition of lipoproteins reduced SR-BI expression in Y1-BS1 cells, an effect that was reversed by administration of cAMP analogs. SR-BI mRNA and protein were expressed at high levels in the adrenal glands of knockout mice lacking the steroidogenic acute regulatory protein; these mice have extensive lipid deposits in the adrenocortical cells and high circulating levels of ACTH. Taken together, these studies suggest that trophic hormones can override the suppressive effect of cholesterol on SR-BI expression, thus ensuring that steroidogenesis is maintained during stress.