Transcriptional regulation of human CYP11A1 in gonads and adrenals.
The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme, also termed cytochrome P450scc, which catalyzes the conversion of cholesterol to pregnenolone in the first step of steroid biosynthesis in mitochondria. The adrenal- and gonad-selective, hormonally and developmentally regulated expression of CYP11A1 is principally driven by its 2.3 kb promoter. Multiple trans-acting factors like SF-1, Sp1, AP-2, TReP-132, LBP-1b, LBP-9, AP-1, NF-1, and Ets control CYP11A1 transcription either through DNA-protein interaction with their specific cis-acting elements or through protein-protein interaction between each other, wherein SF-1 plays a central role in adrenals and testes. In addition to binding with its proximal and upstream motifs, SF-1 also physically interacts with TFIIB, CBP/p300, TReP-132, and c-Jun/AP-1 to specifically transmit the regulatory signals of cAMP. Other factors like Sp1 family members, AP-2, and LBP-1b/LBP-9 may be other factors that play a role in CYP11A1 transcription, particularly in placental cells. The TATA sequence could also contribute to tissue-specificity and hormonal regulation of CYP11A1 transcription. This article reviews recent studies focusing on adrenals and gonads.
Guo
Ing-Cherng
IC
Department of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
Shih
Meng-Chun
MC
Lan
Hsin-Chieh
HC
Hsu
Nai-Chi
NC
Hu
Meng-Chun
MC
Chung
Bon-Chu
BC
D000302:Adrenal Cortex / Q000201:enzymology*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006066:Gonads / Q000201:enzymology*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013256:Steroids / Q000096:biosynthesis; D014158:Transcription, Genetic
D013256:Steroids; D002786:Cholesterol Side-Chain Cleavage Enzyme