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Gene Review

Cyp11a1  -  cytochrome P450, family 11, subfamily a,...

Rattus norvegicus

Synonyms: CYPXIA1, Cholesterol desmolase, Cholesterol side-chain cleavage enzyme, mitochondrial, Cyp11a, Cyp11a-1, ...
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Disease relevance of Cyp11a1

  • The results revealed a decreased expression of mRNA of P450scc enzyme and StAR during nephrosis, and eventhough they increased after gonadotropins treatment, they did not conduce to a normal cycling rat period or fertility recovery [1].
  • C6 rat glioma tumor cells in culture biosynthesize both pregnenolone (P) and D. They possess the mRNA, protein, and side-chain cleavage activity of P450scc [2].
  • We found no effect of either drug on P450scc in intact human choriocarcinoma JEG-3 cells [3].
  • Testicular cholesterol side-chain cleavage enzyme (CSCCE) and delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activities were assessed 12 hours and 2, 4, 8, 16, and 32 days after surgical induction of bilateral cryptorchidism in adult rats [4].
  • In conclusion, this study demonstrates that the expression of P450scc and StAR protein are highly impaired during nephrotic syndrome [5].

Psychiatry related information on Cyp11a1

  • In contrast, non-selective sleep disturbance, resulting in the partial reductions of non-REM and REM sleep, tended to increase both StAR and P450scc mRNA levels without any statistical significance [6].

High impact information on Cyp11a1

  • In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450-dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11 beta-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway [7].
  • The induction of progesterone secretion is observed only after approximately 24 h and closely follows the delayed but quantitatively dramatic induction of the mitochondrial cytochrome P450scc which catalyzes the first step in steroid hormone biosynthesis [8].
  • Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells [8].
  • Taken together with our previous finding of a P450scc-containing neuronal system for pregnenolone synthesis, these results imply that 17beta-estradiol is synthesized by P45017alpha and P450 aromatase localized in hippocampal neurons from endogenous cholesterol [9].
  • A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1) [10].

Chemical compound and disease context of Cyp11a1

  • This study demonstrates that the mechanism by which ovarian steroid biosynthesis is altered during acute nephrosis involves damage at the P450scc and StAR mRNA synthesis and processing [1].
  • P450scc was transcriptionally regulated in Y-1, MA-10, and C6 glioma cells, but not in GC or GT1-7 cells [11].
  • In Experiment 1, naturally-receptive rats received bilateral VTA infusions of a P450scc inhibitor, digitoxin (1 microg/side); a 5alpha-reductase inhibitor, finasteride (10 microg/side); digitoxin (1 microg/side)+finasteride (10 microg/side); or vehicle and were tested 3 h later for lordosis [12].
  • In contrast, the expression of P450scc, a mitochondrial protein, is decreased by Cm but enhanced by ethanol, a powerful elicitor of heat shock response in E. coli [13].

Biological context of Cyp11a1


Anatomical context of Cyp11a1


Associations of Cyp11a1 with chemical compounds


Physical interactions of Cyp11a1

  • Thus, we have demonstrated, for the first time, the presence of PBR and StAR in the pregnant rat CL and that the coordinated suppression of these proteins involved in the mitochondrial cholesterol transport along with P450 scc by GnRH-Ag leads to reduced ovarian steroidogenesis [21].

Regulatory relationships of Cyp11a1


Other interactions of Cyp11a1


Analytical, diagnostic and therapeutic context of Cyp11a1


  1. Steroidogenic impairment due to reduced ovarian transcription of cytochrome P450 side-chain-cleavage (P450scc) and steroidogenic acute regulatory protein (StAR) during experimental nephrotic syndrome. Peña-Rico, M., Guadalupe Ortiz-López, M., Camacho-Castillo, L., Cárdenas, M., Pedraza-Chaverri, J., Menjívar, M. Life Sci. (2006) [Pubmed]
  2. Detection of P450c17-independent pathways for dehydroepiandrosterone (DHEA) biosynthesis in brain glial tumor cells. Cascio, C., Prasad, V.V., Lin, Y.Y., Lieberman, S., Papadopoulos, V. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Medroxyprogesterone acetate and dexamethasone are competitive inhibitors of different human steroidogenic enzymes. Lee, T.C., Miller, W.L., Auchus, R.J. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  4. Influence of experimental cryptorchidism on cholesterol side-chain cleavage enzyme and delta5-3beta-hydroxysteroid dehydrogenase activities in rat testes. Wisner, J.R., Gomes, W.R. Steroids (1978) [Pubmed]
  5. Impaired testicular cytochrome P450 side-chain-cleavage (P450scc) and steroidogenic acute regulatory (StAR) protein expression in rats with nephrotic syndrome. Menjívar, M., Castillo, N., Vilchis, F., Medina-Campos, O.N., Pedraza-Chaverrí, J., Guadalupe Ortiz-López, M. Mol. Cell. Endocrinol. (2003) [Pubmed]
  6. Changes in the expression of steroid metabolism-related genes in rat adrenal glands during selective REM sleep deprivation. Morita, K., Kuwada, A., Fujihara, H., Morita, Y., Sei, H. Life Sci. (2003) [Pubmed]
  7. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. Wagner, R.L., White, P.F., Kan, P.B., Rosenthal, M.H., Feldman, D. N. Engl. J. Med. (1984) [Pubmed]
  8. Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells. Hanukoglu, I., Suh, B.S., Himmelhoch, S., Amsterdam, A. J. Cell Biol. (1990) [Pubmed]
  9. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons. Hojo, Y., Hattori, T.A., Enami, T., Furukawa, A., Suzuki, K., Ishii, H.T., Mukai, H., Morrison, J.H., Janssen, W.G., Kominami, S., Harada, N., Kimoto, T., Kawato, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. 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]
  11. Transcriptional regulation of P450scc gene expression in neural and steroidogenic cells: implications for regulation of neurosteroidogenesis. Zhang, P., Rodriguez, H., Mellon, S.H. Mol. Endocrinol. (1995) [Pubmed]
  12. Inhibiting biosynthesis and/or metabolism of progestins in the ventral tegmental area attenuates lordosis of rats in behavioural oestrus. Petralia, S.M., Jahagirdar, V., Frye, C.A. J. Neuroendocrinol. (2005) [Pubmed]
  13. Protein synthesis inhibitors and ethanol selectively enhance heterologous expression of P450s and related proteins in Escherichia coli. Kusano, K., Waterman, M.R., Sakaguchi, M., Omura, T., Kagawa, N. Arch. Biochem. Biophys. (1999) [Pubmed]
  14. Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system. Hammer, F., Compagnone, N.A., Vigne, J.L., Bair, S.R., Mellon, S.H. Endocrinology (2004) [Pubmed]
  15. Rat cholesterol side-chain cleavage enzyme (P-450scc): use of a cDNA probe to study the hormonal regulation of P-450scc mRNA levels in ovarian granulosa cells. McMasters, K.M., Dickson, L.A., Shamy, R.V., Robischon, K., Macdonald, G.J., Moyle, W.R. Gene (1987) [Pubmed]
  16. Expression of cytochrome P450scc mRNA and protein in the rat kidney from birth to adulthood. Dalla Valle, L., Toffolo, V., Vianello, S., Belvedere, P., Colombo, L. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  17. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism. Slominski, A., Semak, I., Zjawiony, J., Wortsman, J., Li, W., Szczesniewski, A., Tuckey, R.C. FEBS J. (2005) [Pubmed]
  18. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Borch, J., Metzdorff, S.B., Vinggaard, A.M., Brokken, L., Dalgaard, M. Toxicology (2006) [Pubmed]
  19. Systemic administration of alcohol to adult rats inhibits leydig cell activity: Time course of effect and role of nitric oxide. Herman, M., Kang, S.S., Lee, S., James, P., Rivier, C. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  20. Zone-specific regulation of two messenger RNAs for P450c11 in the adrenals of pregnant and nonpregnant rats. Malee, M.P., Mellon, S.H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  21. GnRH agonist treatment decreases progesterone synthesis, luteal peripheral benzodiazepine receptor mRNA, ligand binding and steroidogenic acute regulatory protein expression during pregnancy. Sridaran, R., Philip, G.H., Li, H., Culty, M., Liu, Z., Stocco, D.M., Papadopoulos, V. J. Mol. Endocrinol. (1999) [Pubmed]
  22. Insulin-like growth factor-I selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells. Magoffin, D.A., Kurtz, K.M., Erickson, G.F. Mol. Endocrinol. (1990) [Pubmed]
  23. Interferon-gamma inhibits the steroidogenic acute regulatory protein messenger ribonucleic acid expression and protein levels in primary cultures of rat Leydig cells. Lin, T., Hu, J., Wang, D., Stocco, D.M. Endocrinology (1998) [Pubmed]
  24. Lindane, a gap junction blocker, suppresses FSH and transforming growth factor beta1-induced connexin43 gap junction formation and steroidogenesis in rat granulosa cells. Ke, F.C., Fang, S.H., Lee, M.T., Sheu, S.Y., Lai, S.Y., Chen, Y.J., Huang, F.L., Wang, P.S., Stocco, D.M., Hwang, J.J. J. Endocrinol. (2005) [Pubmed]
  25. Altered ovarian sterol carrier protein expression in the pregnant streptozotocin-treated diabetic rat. McLean, M.P., Warden, K.J., Sandhoff, T.W., Irby, R.B., Hales, D.B. Biol. Reprod. (1996) [Pubmed]
  26. Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Zwain, I.H., Yen, S.S. Endocrinology (1999) [Pubmed]
  27. The acute and chronic effects of adrenocorticotropin on the levels of messenger ribonucleic acid and protein of steroidogenic enzymes in rat adrenal in vivo. Lehoux, J.G., Fleury, A., Ducharme, L. Endocrinology (1998) [Pubmed]
  28. Glucocorticoids and progestins signal the initiation and enhance the rate of myelin formation. Chan, J.R., Phillips, L.J., Glaser, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  29. Pregnenolone biosynthesis in C6-2B glioma cell mitochondria: regulation by a mitochondrial diazepam binding inhibitor receptor. Papadopoulos, V., Guarneri, P., Kreuger, K.E., Guidotti, A., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  30. Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth. Townsend, S.F., Dallman, M.F., Miller, W.L. J. Biol. Chem. (1990) [Pubmed]
  31. Expression of the P450 side-chain cleavage and adrenodoxin genes begins during early stages of adrenal cortex development. Rogler, L.E., Pintar, J.E. Mol. Endocrinol. (1993) [Pubmed]
  32. Transforming growth factor-beta inhibits ovarian 17 alpha-hydroxylase activity by a direct noncompetitive mechanism. Fournet, N., Weitsman, S.R., Zachow, R.J., Magoffin, D.A. Endocrinology (1996) [Pubmed]
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