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CYP11A1  -  cytochrome P450, family 11, subfamily A,...

Homo sapiens

Synonyms: CYP11A, CYPXIA1, Cholesterol desmolase, Cholesterol side-chain cleavage enzyme, mitochondrial, Cytochrome P450 11A1, ...
 
 
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Disease relevance of CYP11A1

 

High impact information on CYP11A1

 

Chemical compound and disease context of CYP11A1

  • Cases of sexual immaturity and male pseudohermaphroditism due to disorders such as androgen resistance, 5 alpha-reductase deficiency, cholesterol desmolase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency, and testicular and ovary dysgenesis can easily be distinguished from 17 alpha-OHD [10].
 

Biological context of CYP11A1

 

Anatomical context of CYP11A1

  • We conclude that CYP11A1 expression in human granulosa cells is regulated by LRH-1 [12].
  • CONCLUSION: This report of a homozygous mutation in CYP11A1 gene in a child with agenesis of corpus callosum shows that homozygous mutations in CYP11A1 gene can be compatible with term pregnancy and delayed presentation [1].
  • The CYP11A1 encodes cytochrome P450scc, catalyzing the first step of steroidogenesis in adrenals and gonads under the control of cAMP-mediated hormonal signals [15].
  • Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria [16].
  • The interactions of CYP11B1 (cytochrome P-45011beta), CYP11B2 (cytochrome P-450aldo) and CYP11A1 (cytochrome P-450scc) were investigated by cotransfection of their cDNA into COS-1 cells [17].
 

Associations of CYP11A1 with chemical compounds

  • The ovine P45 side chain cleavage (CYP11A1) enzyme gene, which catalyzes the initial enzymatic step in steroid hormone biosynthesis is transcriptionally regulated in cultured steroidogenic human trophoblastic JEG-3 cells [11].
  • The first step in human ovarian steroidogenesis is catalyzed by cholesterol side-chain cleavage cytochrome P450 (CYP11A1) enzyme [12].
  • These changes coincide with increased level of CYP11A1 expression in human corpus luteum [12].
  • Activating protein-1 cooperates with steroidogenic factor-1 to regulate 3',5'-cyclic adenosine 5'-monophosphate-dependent human CYP11A1 transcription in vitro and in vivo [15].
  • Four such genes, CYP17, CYP19, CYP11A1, and LH-beta, are involved in the synthesis and conversion of testosterone to dihydrotestosterone and estradiol [18].
 

Physical interactions of CYP11A1

  • The promoter of the CYP11A1 gene contains sequences that bind to transcription factor SF-1, which plays an important role in the tissue-specific and hormonally regulated expression of steroidogenic genes [19].
 

Enzymatic interactions of CYP11A1

  • Isolated murine MSCs transfected with green fluorescence protein driven by the promoter of P450 side-chain cleaving enzyme gene (CYP11A), a steroidogenic cell-specific gene, were used to detect steroidogenic cell production in vitro [20].
 

Regulatory relationships of CYP11A1

  • Expression of the ovine P-450 side-chain cleavage enzyme gene (CYP11A1) is stimulated by epidermal growth factor (EGF) through a pathway that involves c-Jun in JEG-3 placental cells [21].
  • In the current studies, AP-2 induced the ovine CYP11A1 promoter 4.5-fold in JEG-3 cells with full induction requiring the previously defined cAMP-responsive elements [11].
  • A novel zinc finger protein TReP-132 interacts with CBP/p300 to regulate human CYP11A1 gene expression [22].
  • These studies indicate that insulin exerts a selective inhibitory effect on cytotrophoblastic aromatase activity, whereas IGF-I inhibits aromatase activity but stimulates P450 SCC activity [23].
  • Detailed transcriptional analysis documents the importance of SF-1 in activating CYP11A1 in vitro and in vivo [19].
 

Other interactions of CYP11A1

  • CYP1B1 mRNA was elevated by a 2-day adrenocorticotropic hormone treatment but much less than CYP11A1 (cytochrome P450 side chain cleavage) mRNA (2-fold versus 4-fold) [24].
  • In this study, we examined the role of LRH-1 in the regulation of human granulosa cell CYP11A1 expression [12].
  • The competition of human CYP11A1 with human CYP11B1 and CYP11B2 could be diminished with excess expression of bovine adrenodoxin [17].
  • We investigated the intracellular signaling pathways governing EGF induction of the CYP11A1 promoter [21].
  • Mutation of the EGF-RE AP-1-like sequence in the context of the native promoter reduced CYP11A1 promoter activation by ras 60% [21].
 

Analytical, diagnostic and therapeutic context of CYP11A1

References

  1. Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum. al Kandari, H., Katsumata, N., Alexander, S., Rasoul, M.A. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  2. Autoantibodies against CYP2D6 and other drug-metabolizing enzymes in autoimmune hepatitis type 2. Mizutani, T., Shinoda, M., Tanaka, Y., Kuno, T., Hattori, A., Usui, T., Kuno, N., Osaka, T. Drug Metab. Rev. (2005) [Pubmed]
  3. Molecular genetics of congenital adrenal hyperplasia. White, P.C., New, M.I. Baillieres Clin. Endocrinol. Metab. (1988) [Pubmed]
  4. Microsatellite polymorphism of steroid hormone synthesis gene CYP11A1 is associated with advanced prostate cancer. Kumazawa, T., Tsuchiya, N., Wang, L., Sato, K., Kamoto, T., Ogawa, O., Nakamura, A., Kato, T., Habuchi, T. Int. J. Cancer (2004) [Pubmed]
  5. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Guryev, O., Carvalho, R.A., Usanov, S., Gilep, A., Estabrook, R.W. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. MLN64 contains a domain with homology to the steroidogenic acute regulatory protein (StAR) that stimulates steroidogenesis. Watari, H., Arakane, F., Moog-Lutz, C., Kallen, C.B., Tomasetto, C., Gerton, G.L., Rio, M.C., Baker, M.E., Strauss, J.F. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. Cloning and expression of a cDNA encoding human sterol carrier protein 2. Yamamoto, R., Kallen, C.B., Babalola, G.O., Rennert, H., Billheimer, J.T., Strauss, J.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  8. Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Chung, B.C., Matteson, K.J., Voutilainen, R., Mohandas, T.K., Miller, W.L. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  9. Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Gharani, N., Waterworth, D.M., Batty, S., White, D., Gilling-Smith, C., Conway, G.S., McCarthy, M., Franks, S., Williamson, R. Hum. Mol. Genet. (1997) [Pubmed]
  10. 17 alpha-hydroxylation deficiency. Biglieri, E.G., Kater, C.E. Endocrinol. Metab. Clin. North Am. (1991) [Pubmed]
  11. Activator protein-2 mediates transcriptional activation of the CYP11A1 gene by interaction with Sp1 rather than binding to DNA. Pena, P., Reutens, A.T., Albanese, C., D'Amico, M., Watanabe, G., Donner, A., Shu, I.W., Williams, T., Pestell, R.G. Mol. Endocrinol. (1999) [Pubmed]
  12. The orphan nuclear receptor, liver receptor homolog-1, regulates cholesterol side-chain cleavage cytochrome p450 enzyme in human granulosa cells. Kim, J.W., Havelock, J.C., Carr, B.R., Attia, G.R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  13. Genetic linkage mapping of the CYP11A1 gene encoding the cholesterol side-chain cleavage P450scc close to the CYP1A1 gene and D15S204 in the chromosome 15q22.33-q23 region. Durocher, F., Morissette, J., Simard, J. Pharmacogenetics (1998) [Pubmed]
  14. Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts. Yang, R., You, X., Tang, X., Gao, L., Ni, X. J. Mol. Endocrinol. (2006) [Pubmed]
  15. Activating protein-1 cooperates with steroidogenic factor-1 to regulate 3',5'-cyclic adenosine 5'-monophosphate-dependent human CYP11A1 transcription in vitro and in vivo. Guo, I.C., Huang, C.Y., Wang, C.K., Chung, B.C. Endocrinology (2007) [Pubmed]
  16. Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria. Derouet-Hümbert, E., Roemer, K., Bureik, M. Biol. Chem. (2005) [Pubmed]
  17. Interaction of CYP11B1 (cytochrome P-45011 beta) with CYP11A1 (cytochrome P-450scc) in COS-1 cells. Cao, P.R., Bernhardt, R. Eur. J. Biochem. (1999) [Pubmed]
  18. Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta. Douglas, J.A., Zuhlke, K.A., Beebe-Dimmer, J., Levin, A.M., Gruber, S.B., Wood, D.P., Cooney, K.A. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  19. Transcriptional regulation of CYP11A1. Guo, I.C., Hu, M.C., Chung, B.C. J. Biomed. Sci. (2003) [Pubmed]
  20. Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells. Yazawa, T., Mizutani, T., Yamada, K., Kawata, H., Sekiguchi, T., Yoshino, M., Kajitani, T., Shou, Z., Umezawa, A., Miyamoto, K. Endocrinology (2006) [Pubmed]
  21. Stimulation of the P-450 side chain cleavage enzyme (CYP11A1) promoter through ras- and Ets-2-signaling pathways. Pestell, R.G., Albanese, C., Watanabe, G., Lee, R.J., Lastowiecki, P., Zon, L., Ostrowski, M., Jameson, J.L. Mol. Endocrinol. (1996) [Pubmed]
  22. A novel zinc finger protein TReP-132 interacts with CBP/p300 to regulate human CYP11A1 gene expression. Gizard, F., Lavallée, B., DeWitte, F., Hum, D.W. J. Biol. Chem. (2001) [Pubmed]
  23. Modulation of aromatase and P450 cholesterol side-chain cleavage enzyme activities of human placental cytotrophoblasts by insulin and insulin-like growth factor I. Nestler, J.E. Endocrinology (1987) [Pubmed]
  24. Identification of a rat adrenal cytochrome P450 active in polycyclic hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue-specific pattern of hormonal and aryl hydrocarbon receptor-linked regulation. Bhattacharyya, K.K., Brake, P.B., Eltom, S.E., Otto, S.A., Jefcoate, C.R. J. Biol. Chem. (1995) [Pubmed]
  25. Bone morphogenetic protein inhibits ovarian androgen production. Dooley, C.A., Attia, G.R., Rainey, W.E., Moore, D.R., Carr, B.R. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  26. Molecular cloning and characterization of the cyclic AMP-responsive ovine CYP11A1 (cholesterol side-chain cleavage) gene promoter: DNase 1 protection of conserved consensus elements. Pestell, R.G., Hammond, V.E., Crawford, R.J. J. Mol. Endocrinol. (1993) [Pubmed]
  27. Expression of P450 side-chain cleavage (CYP11A1) and P450 17alpha-hydroxylase-17/20 lyase (CYP17) messenger ribonucleic acid in hamster primary interstitial cells in vitro: differential regulation of steroidogenesis by cyclic adenosine monophosphate. Schwartz, J.R., Roy, S.K. Biol. Reprod. (2000) [Pubmed]
  28. The post-menopausal ovary displays a unique pattern of steroidogenic enzyme expression. Havelock, J.C., Rainey, W.E., Bradshaw, K.D., Carr, B.R. Hum. Reprod. (2006) [Pubmed]
 
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