Sugawara T, Holt J A, Driscoll D, Strauss J F, Lin D, Miller W L, Patterson D, Clancy K P, Hart I M, Clark B J
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia 19104, USA.
Proc Natl Acad Sci U S A. 1995 May 23;92(11):4778-82. doi: 10.1073/pnas.92.11.4778.
Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.
类固醇生成急性调节蛋白(StAR)似乎介导了促性腺激素刺激的孕烯醇酮合成的快速增加。从人肾上腺皮质文库中分离出编码StAR的cDNA。在COS-1细胞中与细胞色素P450scc和肾上腺皮质铁氧化还原蛋白共表达的人StAR,使孕烯醇酮合成增加了4倍以上。在卵巢和睾丸中检测到一条1.6 kb的主要StAR转录本以及4.4 kb和7.5 kb含量较少的转录本。肾脏中1.6 kb信息的含量较低。在包括胎盘在内的其他组织中未检测到StAR mRNA。用8-溴腺苷3',5'-环磷酸处理颗粒细胞24小时可使StAR mRNA增加3倍或更多。使用体细胞杂交定位板将编码StAR的结构基因定位到8号染色体短臂。荧光原位杂交将StAR基因座定位在8p11.2区域。一个StAR假基因被定位到13号染色体。我们得出结论,StAR的表达仅限于进行线粒体甾醇氧化且受cAMP急性调节的组织,并且StAR mRNA水平受cAMP调节。