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Gene Review

Cyp17a1  -  cytochrome P450, family 17, subfamily a,...

Mus musculus

Synonyms: 17-alpha-hydroxyprogesterone aldolase, CYPXVII, Cyp17, Cytochrome P450 17A1, Cytochrome P450-C17, ...
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Disease relevance of Cyp17a1

  • This results from higher levels of steroidogenic activity per fetal Leydig cell, as indicated by the hypertrophy of these cells and the higher levels of mRNA for StAR, P450c17 and P450scc in the testis, for a similar number of Leydig cells [1].
  • Steroidogenic enzymes P450scc, P450c17 and P450c21 have recently been shown to be the main autoantigens recognized by sera from patients with autoimmune polyglandular syndrome (APS type I) with or without Addison's disease [2].

High impact information on Cyp17a1

  • There was also a slight decrease in 17-OH-progesterone compared to the more significant decrease in testosterone, suggesting that MIS might be regulating the lyase activity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its hydroxylase activity [3].
  • These data suggest that steroid products of P450c17 have heretofore-unknown essential functions in early embryonic mouse development [4].
  • The synthesis of DHEA and sex steroids, but not mouse glucocorticoids and mineralocorticoids, requires P450c17, which catalyzes both 17 alpha-hydroxylase and 17,20-lyase activities [4].
  • Immunocytochemistry identified P450c17 in embryonic endoderm in E7 wild-type and heterozygous embryos, but its function in these cells is unknown [4].
  • Heterozygotes were phenotypically and reproductively normal, but in all mouse lines, P450c17(-/-) zygotes died by embryonic day 7, prior to gastrulation [4].

Biological context of Cyp17a1


Anatomical context of Cyp17a1


Associations of Cyp17a1 with chemical compounds

  • The inhibition of testosterone production is parallel to the inhibition of P450c17 messenger RNA and protein levels [11].
  • These data suggest that the absence of fetal ovarian steroid hormone production is the result of lack of expression of at least three of the steroidogenic enzymes, P450scc, P450c17, and P450arom [12].
  • On the other hand, both proopiomelanocortin-derived peptide beta-endorphin and corticosterone concentration levels are elevated in Wnt-deficient mice, and the expression of Cyp17 is altered in Wnt-4 mutant females, so that it mimics the pattern specific for males [13].
  • The methodology was verified by confirming the presence of previously characterized TP-regulated genes, including Pem in Sertoli cells and Cyp17a1 in Leydig cells [14].
  • Northern analysis showed that, in both MIS-treated rats and mice, the mRNA for Cyp17, which catalyzes the committed step in androgen synthesis, was down-regulated [3].

Physical interactions of Cyp17a1


Regulatory relationships of Cyp17a1


Other interactions of Cyp17a1


Analytical, diagnostic and therapeutic context of Cyp17a1


  1. Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor alpha. Delbès, G., Levacher, C., Duquenne, C., Racine, C., Pakarinen, P., Habert, R. Endocrinology (2005) [Pubmed]
  2. Characterization of adrenal autoantigens recognized by sera from patients with autoimmune polyglandular syndrome (APS) type I. Uibo, R., Perheentupa, J., Ovod, V., Krohn, K.J. J. Autoimmun. (1994) [Pubmed]
  3. Müllerian Inhibiting Substance lowers testosterone in luteinizing hormone-stimulated rodents. Trbovich, A.M., Sluss, P.M., Laurich, V.M., O'Neill, F.H., MacLaughlin, D.T., Donahoe, P.K., Teixeira, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Deletion of the mouse P450c17 gene causes early embryonic lethality. Bair, S.R., Mellon, S.H. Mol. Cell. Biol. (2004) [Pubmed]
  5. Müllerian inhibiting substance blocks the protein kinase A-induced expression of cytochrome p450 17alpha-hydroxylase/C(17-20) lyase mRNA in a mouse Leydig cell line independent of cAMP responsive element binding protein phosphorylation. Laurich, V.M., Trbovich, A.M., O'Neill, F.H., Houk, C.P., Sluss, P.M., Payne, A.H., Donahoe, P.K., Teixeira, J. Endocrinology (2002) [Pubmed]
  6. Developmentally regulated expression of adrenal 17 alpha-hydroxylase cytochrome P450 in the mouse embryo. Keeney, D.S., Jenkins, C.M., Waterman, M.R. Endocrinology (1995) [Pubmed]
  7. Isolation and characterization of the mouse P450 17 alpha-hydroxylase/C17-20-lyase gene (Cyp17): transcriptional regulation of the gene by cyclic adenosine 3',5'-monophosphate in MA-10 Leydig cells. Youngblood, G.L., Payne, A.H. Mol. Endocrinol. (1992) [Pubmed]
  8. Repression of cAMP-induced expression of the mouse P450 17 alpha-hydroxylase/C17-20 lyase gene (Cyp17) by androgens. Burgos-Trinidad, M., Youngblood, G.L., Maroto, M.R., Scheller, A., Robins, D.M., Payne, A.H. Mol. Endocrinol. (1997) [Pubmed]
  9. The role of tumor necrosis factor-alpha in the regulation of mouse Leydig cell steroidogenesis. Xiong, Y., Hales, D.B. Endocrinology (1993) [Pubmed]
  10. Novel role for the nuclear phosphoprotein SET in transcriptional activation of P450c17 and initiation of neurosteroidogenesis. Compagnone, N.A., Zhang, P., Vigne, J.L., Mellon, S.H. Mol. Endocrinol. (2000) [Pubmed]
  11. Tumor necrosis factor-alpha inhibition of 17 alpha-hydroxylase/C17-20 lyase gene (Cyp17) expression. Li, X., Youngblood, G.L., Payne, A.H., Hales, D.B. Endocrinology (1995) [Pubmed]
  12. Ontogeny of expression of the genes for steroidogenic enzymes P450 side-chain cleavage, 3 beta-hydroxysteroid dehydrogenase, P450 17 alpha-hydroxylase/C17-20 lyase, and P450 aromatase in fetal mouse gonads. Greco, T.L., Payne, A.H. Endocrinology (1994) [Pubmed]
  13. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Heikkilä, M., Peltoketo, H., Leppäluoto, J., Ilves, M., Vuolteenaho, O., Vainio, S. Endocrinology (2002) [Pubmed]
  14. Androgen-regulated transcripts in the neonatal mouse testis as determined through microarray analysis. Zhou, Q., Shima, J.E., Nie, R., Friel, P.J., Griswold, M.D. Biol. Reprod. (2005) [Pubmed]
  15. Consensus sequence of transcription factor SF-1 binding site and putative binding site in the 5' flanking regions of genes encoding mouse steroidogenic enzymes 3betaHSDI and Cyp17. Busygina, T.V., Ignatieva, E.V., Osadchuk, A.V. Biochemistry Mosc. (2003) [Pubmed]
  16. Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens. Houk, C.P., Pearson, E.J., Martinelle, N., Donahoe, P.K., Teixeira, J. Endocrinology (2004) [Pubmed]
  17. Arginine vasopressin inhibition of cytochrome P450c17 and testosterone production in mouse Leydig cells. Hales, D.B., Greene, R. Endocrine (1998) [Pubmed]
  18. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. Couse, J.F., Yates, M.M., Walker, V.R., Korach, K.S. Mol. Endocrinol. (2003) [Pubmed]
  19. Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice. Wu, X., Arumugam, R., Baker, S.P., Lee, M.M. Endocrinology (2005) [Pubmed]
  20. Scraggly, a new hair loss mutation on mouse chromosome 19. Herron, B.J., Bryda, E.C., Heverly, S.A., Collins, D.N., Flaherty, L. Mamm. Genome (1999) [Pubmed]
  21. Effects of 3,3',4,4',5-pentachlorobiphenyl, a coplanar polychlorinated biphenyl congener, on cultured neonatal mouse testis. Fukuzawa, N.H., Ohsako, S., Nagano, R., Sakaue, M., Baba, T., Aoki, Y., Tohyama, C. Toxicology in vitro : an international journal published in association with BIBRA. (2003) [Pubmed]
  22. Nitric oxide is a mediator of the inhibitory effect of activated macrophages on production of androgen by the Leydig cell of the mouse. Pomerantz, D.K., Pitelka, V. Endocrinology (1998) [Pubmed]
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