Skip to main content

Regulation of Steroidogenic and Related P450s

  • Chapter
Cytochrome P450

Abstract

One broad classification of P450s is as two groups, one containing forms that metabolize endogenous substrates and the other, forms that metabolize exogenous substrates (xenobiotics). Those forms that metabolize endogenous substrates generally convert less active compounds into more active ones. This is particularly true of the P450s that participate in steroid hormone biosynthesis, where the less active steroid cholesterol is converted into more active mineralocorticoids, glucocorticoids, progestins, and sex hormones. Interestingly, hepatic P450s of the xenobiotic-metabolizing class may play important roles in inactivating these steroid hormones. In the case of vitamin D we also find that distinct P450s play roles in producing the most active forms of this hormone and other P450s are important in their inactivation. This chapter will summarize our understanding of the function and regulation of P450 systems involved in production of active steroids and related compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Simpson, E. R., 1979, Cholesterol side-chain cleavage cytochrome P450 and the control of steroidogenesis, Mol. Cell. Endocrinol. 13: 213–227.

    Article  PubMed  CAS  Google Scholar 

  2. Jefcoate, C. R., McNamara, B. C., Artemenko, I., and Yamazaki, T., 1992, Regulation of cholesterol movement to mitochondrial cytochrome P450scc in steroid hormone synthesis, J. Steroid Biochem. Mol. Biol. 43: 751–767.

    Article  PubMed  CAS  Google Scholar 

  3. DuBois, R. N., Simpson, E. R., Tuckey, J., Lambeth, J. D., and Waterman, M. R., 1981, Evidence for a higher molecular weight precursor of cholesterol side chain cleavage cytochrome P450 and induction of mitochondria! and cytosolic proteins by ACTH in adult bovine adrenal cells, Proc. Natl. Acad. Sci. USA 78: 1028–1032.

    Article  PubMed  CAS  Google Scholar 

  4. Matocha, M. F., and Waterman, M. R., 1985, Synthesis and processing of mitochondrial steroid hydroxylases. In vivo maturation of the precursor forms of cytochrome P450scc, P4501113 and adrenodoxin, J. Biol. Chem. 260: 12259–12265.

    Google Scholar 

  5. Sakaguchi, M., Mihara, K., and Sato, R., 1987, A short amino-terminal segment of microsomal cytochrome P450 functions both as an insertion signal and as a stop-transfer sequence, EMBO J. 6: 2425–2431.

    CAS  Google Scholar 

  6. Clark, B. J., and Waterman, M. R., 1991, The folding of bovine 17a-hydroxylase into a functional hemoprotein in COS 1 cells requires the hydrophobic amino terminal sequence, J. Biol. Chem. 266: 5898–5904.

    PubMed  CAS  Google Scholar 

  7. Clark, B. J., and Waterman, M. R., 1992, Functional expression of bovine 17a-hydroxylase in COS 1 cells is dependent upon the presence of an amino-terminal signal anchor sequence, J. Biol. Chem. 267: 24568–24574.

    PubMed  CAS  Google Scholar 

  8. Shimozawa, O., Salcaguchi, M., Ogawa, H., Harada, N., Mihara, K., and Omura, T., 1993, Core glycosylation of cytochrome P450(arom), J. Biol. Chem. 268: 21399–21402.

    PubMed  CAS  Google Scholar 

  9. Amarneh, B., Corbin, C. J., Peterson, J. A., Simpson, E. R., and Graham-Lorene, S., 1993, Functional domains of human aromatase cytochrome P450 characterized by molecular modelling and site-directed mutagenesis, Mol. Endocrinol. 7: 1617–1624.

    Article  PubMed  CAS  Google Scholar 

  10. Rodgers, R. J., Waterman, M. R., and Simpson, E. R., 1986, Cytochromes P450scc, P45017a, adrenodoxin and reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 reductase in bovine follicles and corpora lutea. Changes in specific contents during the ovarian cycle, Endocrinology 118: 1366–1374.

    Article  PubMed  CAS  Google Scholar 

  11. Lambeth, J. D., Kitchen, S. E., and Farooqui, A. A., 1982, Cytochrome P450scc—substrate interactions, J. Biol. Chem. 257: 1876–1884.

    PubMed  CAS  Google Scholar 

  12. Nakajin, S., Shinoda, M., Haniu, M., Shively, J. E., and Hall, P. F., 1984, C21 steroid side chain cleavage enzyme from porcine adrenal microsomes, J. Biol. Chem. 259: 3971–3976.

    PubMed  CAS  Google Scholar 

  13. Zuber, M. X., Simpson, E. R., and Waterman, M. R., 1986, Expression of bovine 17a-hydroxylase cytochrome P450 cDNA in non-steroidogenic (COS 1) cells, Science 234: 1258–1261.

    Article  PubMed  CAS  Google Scholar 

  14. Ivan, H., and Tamaoki, B.-i., 1978, In vitro effect of 16a-hydroxyprogesterone on the enzyme activities related to androgen production in human testes, Acta Endocrinol. 88: 768–777.

    Google Scholar 

  15. Fevold, H. R., Lorence, M. C., McCarthy, J. L., Trant, J. M., Kagimoto, M., Waterman, M. R., and Mason, J. I., 1989, Rat testis P45017a: Characterization of a full-length cDNA encoding a unique steroid hydroxylase capable of catalyzing both P4 and P5–17,20-lyase reactions, Mol. Endocrinol. 3: 968–976.

    Article  PubMed  CAS  Google Scholar 

  16. Mason, J. I., and Estabrook, R. W., 1973, Testicular cytochrome P450 and iron—sulfur protein as related to steroid metabolism, Ann. N.Y Acad. Sci. 212: 406–419.

    Article  PubMed  CAS  Google Scholar 

  17. Katagiri, M., Kagawa, N., and Waterman, M. R., 1994, The role of cytochrome b5 in the biosynthesis of androgens by human P450c17, Arch. Biochem. Biophys. 317: 343–347

    Article  Google Scholar 

  18. Schlinger, B. A., and Arnold, A. P., 1991, Brain is the major site of estrogen synthesis in a male songbird, Proc. Natl. Acad. Sci. USA 88: 4191–4194.

    Article  PubMed  CAS  Google Scholar 

  19. Johnson, E. F., Kronback, T., and Hsu, M.-H.,1992, Analysis of the catalytic specificity of cytochrome P450 enzymes through site-directed mutagenesis, FASEB J. 6: 700–705.

    Google Scholar 

  20. Ogishima, T., Mitani, F., and Ishimura, Y., 1989, Isolation of aldosterone synthase cytochrome P450 from zona glomerulosa mitochondria of rat adrenal cortex, J. Biol. Chem. 264: 10935–10938.

    PubMed  CAS  Google Scholar 

  21. Ogishima, T., Mitani, F., and Ishimura, Y., 1989, Isolation of two distinct cytochromes P45011ß with aldosterone synthase activity from bovine adrenocortical mitochondria, J. Biochem. 105: 497–499.

    PubMed  CAS  Google Scholar 

  22. Ikeda, Y., Shen, W.-H., Ingraham, H. A., and Parker, K. L., 1994, Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylases, Mol. Endocrinol. 8: 654–662.

    Article  PubMed  CAS  Google Scholar 

  23. Waterman, M. R., and Keeney, D. S., 1992, Genes involved in androgen biosynthesis and the male phenotype, Harm. Res. 38: 217–221.

    Article  CAS  Google Scholar 

  24. Yang, X., Iwamoto, K., Wang, M., Artwohl, J., Mason, J. I., and Pang, S., 1993, Inherited congenital adrenal hyperplasia in the rabbit is caused by a deletion in the gene encoding cytochrome P450 cholesterol side-chain cleavage enzyme, Endocrinology 132: 1977–1982.

    Article  PubMed  CAS  Google Scholar 

  25. Sakai, Y., Yanase, T., Okabe, Y., Hara, T., Waterman, M. R., Takayanagi, R., Haji, J., and Nawata, N., 1994, No mutation in cytochrome P450scc in a patient with congenital lipoid adrenal hyperplasia, J. Clin. Endocrinol. Metab. 79: 1198–1201.

    Article  PubMed  CAS  Google Scholar 

  26. Luo, X., Ikeda, Y., and Parker, K. L., 1994, A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation, Cell 77: 481–490.

    Article  PubMed  CAS  Google Scholar 

  27. Lund, J., Faucher, D. J., Ford, S. P., Porter, J. C., Waterman, M. R., and Mason, J. I., 1988, Developmental expression of bovine adrenocortical steroid hydroxylases: Regulation of P45017a expression leads to episodic fetal cortisol production,. 1. Biol. Chem. 263: 16195–16201.

    CAS  Google Scholar 

  28. Ikeda, Y., Lala, D. S., Luo, X., Kim, E., Moisan, M.-P., and Parker, K. L., 1993, Characterization of the mouse FTZ-Fl gene, which encodes a key regulator of steroid hydroxylase gene expression, Mol. Endocrinol. 7: 852–860.

    Article  PubMed  CAS  Google Scholar 

  29. Honda, S., Morohashi, K., Nomura, M., Takeya, M., Kitajimi, M., and Omura, T., 1993, Ad4BP regulating steroidogenic P450 genes is a member of steroid hormone receptor superfamily, J. Biol. Chem. 268: 7479–7502.

    Google Scholar 

  30. Rodgers, R. J., Waterman, M. R., and Simpson, E. R., 1987, Levels of messenger ribonucleic acid encoding cholesterol side chain cleavage cytochrome P450, 17a-hydroxylase cytochrome P450, adrenodoxin, and low density lipoprotein receptor in bovine follicles and corpora lutea throughout the ovarian cycle, Mol. Endocrinol. 1: 274–279.

    Article  PubMed  CAS  Google Scholar 

  31. Barnhart, K. M., and Mellon, P. L., 1994, The orphan nuclear receptor, steroidogenic factor-1, regulates the glycoprotein hormone a-subunit gene in pituitary gonadotropes, Mol. Endocrinol. 8: 878–885.

    Article  PubMed  CAS  Google Scholar 

  32. Mellon, S. H., and Deschepper, C. F., 1993, Neurosteroid biosynthesis: Genes for adrenal steroidogenic enzymes are expressed in the brain, Brain Res. 629: 283–292.

    Article  PubMed  CAS  Google Scholar 

  33. Lauber, M. E., and Lichtensteiger, W., 1994, Pre-and postnatal ontogeny of aromatase cytochrome P450 messenger ribonucleic acid expression in the male rat brain studied by in situ hybridization, Endocrinology 135: 1661–1668.

    Article  PubMed  CAS  Google Scholar 

  34. Simpson, E. R., and Waterman, M. R., 1988, Action of ACTH to regulate the synthesis of steroidogenic enzymes in adrenal cortical cells, Annu. Rev. Physiol. 50: 427–440.

    Article  PubMed  CAS  Google Scholar 

  35. Clark, B. J., Wells, J., King, S. R., and Stocco, D. M., 1994, The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondria] protein in MA-10 mouse Leydig tumor cells, J. Biol. Chem. 269: 28318–28322.

    Google Scholar 

  36. Waterman, M. R., and Simpson, E. R., 1989, Regulation of steroid hydroxylase gene expression is multifactorial in nature, Recent Prog. Horm. Res. 45: 533–566.

    PubMed  CAS  Google Scholar 

  37. Brentano, S. T., Picado-Leonard, J., Mellon, S. H., Moore, C. C. D., and Miller, W. L., 1990, Tissue-specific, cyclic adenosine 3’,5’-monophosphate-induced, and phorbol ester-repressed transcription from the human P450c17 promoter in mouse cells, Mol. Endocrinol. 4: 1972–1979.

    Article  PubMed  CAS  Google Scholar 

  38. Bakke, M., and Lund, J., 1992, A novel 3’,5’-cyclic adenosine monophosphate-responsive sequence in the bovine CYP17 gene is a target of negative regulation by protein kinase C, Mol. Endocrinol. 6: 1323–1331.

    Article  PubMed  CAS  Google Scholar 

  39. Hanukoglu, I., Feuchtwanger, R., and Hanukoglu, A., 1990, Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells, J. Biol. Chem. 265: 20602–20608.

    PubMed  CAS  Google Scholar 

  40. Enyeart, J. J., Mlinar, B., and Enyeart, J. A., 1993, T-Type Ca’+ channels are required for adrenocorticotropin-stimulated cortisol production by bovine adrenal zona fasciculata cells, Mol. Endocrinol. 7: 1031–1040.

    Article  PubMed  CAS  Google Scholar 

  41. Kimura, T., 1969, Effects of hypophysectomy and ACTH administration on the level of adrenal cholesterol side-chain desmolase, Endocrinology 85: 492–499.

    Article  PubMed  CAS  Google Scholar 

  42. Purvis, J. L., Canick, J. A., Latif, S. A., Rosenbaum, J. H., Hologgitar, J., and Menard, R. H., 1973, Lifetime of microsomal cytochrome P450 and steroidogenic enzymes in rat testis as influenced by human chorionic gonadotropin, Arch. Biochem. Biophys. 159: 39–49.

    Article  PubMed  CAS  Google Scholar 

  43. Purvis, J. L., Canick, J. A., Mason, J. I., Estabrook, R. W., and McCarthy, J. L., 1973, Lifetime of adrenal cytochrome P450 as influenced by ACTH, Ann. N.Y. Acad. Sci. 212: 319–342.

    Article  PubMed  CAS  Google Scholar 

  44. John, M. E., John, M. C., Boggaram, V., Simpson, E. R., and Waterman, M. R., 1986, Transcriptional regulation of steroid hydroxylase genes by corticotropin, Proc. Nat!. Acad. Sci. USA 83: 4715–4719.

    Article  PubMed  CAS  Google Scholar 

  45. Roesler, W. J., Vandenbar, G. R., and Hanson, R. W., 1988, Cyclic AMP and the induction of eucaryotic gene transcription, J. Biol. Chem. 263: 9063–9066.

    PubMed  CAS  Google Scholar 

  46. Kagawa, N., and Waterman, M. R., 1991, Evidence that an adrenal-specific nuclear protein regulates cAMP responsiveness of the human CYP21B (P450c21) gene, J. Biol. Chem. 266: 11199–11204.

    PubMed  CAS  Google Scholar 

  47. Kagawa, N., and Waterman, M. R., 1992, Purification and characterization of a transcription factor which appears to regulate cAMP responsiveness of the human CYP21B gene, J. Biol. Chem. 267: 21213–21219.

    Google Scholar 

  48. Zanger, U. M., Kagawa, N., Lund, J., and Waterman, M. R., 1992, Distinct biochemical mechanisms for cAMP-dependent transcription of CYP17 and CYP21, FASEB J. 6: 713–719.

    Google Scholar 

  49. Momoi, K., Waterman, M. R., Simpson, E. R., and Zanger, U. M., 1992, 3’,5’-Cyclic adenosine monophosphate-dependent transcription of the CYP11 A (cholesterol side chain cleavage cytochrome P450) gene involves a DNA response element containing a putative binding site for transcription factor Spl, Mol. Endocrino. 6: 1682–1690.

    Google Scholar 

  50. Lund, J., Ahlgren, R., Wu, D., Kagimoto, M., Simpson, E. R., and Waterman, M. R., 1990, Transcriptional regulation of the bovine CYP17 (P45017a) gene, J. Biol. Chem. 265: 3304–3312.

    PubMed  CAS  Google Scholar 

  51. Zuber, M. X., John, M. E., Olcamura, T., Simpson, E. R., and Waterman, M. R., 1986, Bovine adrenocortical cytochrome P45017a, regulation of gene expression by ACTH and elucidation of primary sequence, J. Biol. Chem. 261: 2475–2482.

    PubMed  CAS  Google Scholar 

  52. Bakke, M., and Lund, J., 1994, Mutually exclusive interactions of two nuclear orphan receptors determine activity of a cAMP-responsive sequence in the bovine CYP17 gene, Mol. Endocrino. 9: 327–339.

    Article  Google Scholar 

  53. Kagawa, N., Ogo, A., Takahashi, Y., Iwamatsu, A., and Waterman, M. R., 1994, A cAMP-responsive sequence (CRS I) of CYP17 is a cellular target for the homeodomain protein Pbxl, J. Biol. Chem. 269: 18716–18719.

    PubMed  CAS  Google Scholar 

  54. Monica, K., Galili, N., Nourse, J., Saltman, D., and Cleary, M. L., 1991, PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1, Mol. Cell. Biol. 11: 6149–6157.

    PubMed  CAS  Google Scholar 

  55. Ahlgren, R., Simpson, E. R., Waterman, M. R., and Lund, J., 1990, Characterization of the promoter/regulatory region of the bovine CYP11A (P450scc) gene: Basal and cAMP-dependent expression, J. Biol. Chem. 265: 3313–3319.

    PubMed  CAS  Google Scholar 

  56. Venepally, P., and Waterman, M. R., 1994, Two Spl -binding sites mediate cAMP-induced transcription of the bovine CYP11Agene through the protein kinase Apathway, J. Biol. Chem. submitted for publication.

    Google Scholar 

  57. Honda, S., Morohashi, K., and Omura, T., 1990, Novel cAMP regulatory elements in the promoter region of bovine P45011ß gene, J. Biochem. 108: 1042–1049.

    PubMed  CAS  Google Scholar 

  58. Chen, J.-Y., and Waterman, M. R., 1992, Two promoters in the bovine adrenodoxin gene and the role of associated, unique cAMP-responsive sequences, Biochemistry 31: 2400–2407.

    Article  PubMed  CAS  Google Scholar 

  59. Rice, D. A., Aitken, L. D., Vandenbark, G. R., Mouw, A. R., Franklin, A., Schimmer, B. P., and Parker, K. L., 1989, A CAMP-responsive element regulates expression of the mouse steroid 11P-hydroxylase gene, J. Biol. Chem. 264: 14011–14015.

    PubMed  CAS  Google Scholar 

  60. Domalik, L. J., Chaplin, D. D., Kirkman, M. S., Wu, R. C., Liu, W. W., Howard, T. A., Seldin, M. F., and Parker, K. L., 1991, Different isozymes of mouse 1113-hydroxylase produce mineralocorticoids and glucocorticoids, Mol. Endocrinol. 5: 1853–1861.

    Article  PubMed  CAS  Google Scholar 

  61. Chang, C.-Y., Huang, C., Guo, I.-C., Tsai, H.-M., Wu, D.-A., and Chung, B.-C., 1992, Transcription of the human ferredoxin gene through a single promoter which contains the 3’,5’-cyclic adenosine monophosphate-responsive sequence and SP1-binding site, Mol. Endocrinol. 6: 1362–1370.

    Article  PubMed  CAS  Google Scholar 

  62. Guo, I.-C., Tsai, H.-M., and Chung, B.-C., 1994, Actions of two different cAMP-responsive sequence and an enhancer of the human CYP11A1 (P450scc) gene in adrenal Y1 and placenta JEG-3 cells, J. Biol. Chem. 269: 6362–6369.

    PubMed  CAS  Google Scholar 

  63. Rice, D. A., Kirkman, M. S., Aitken, L. D., Mouw, A. R., Schimmer, B. P., and Parker, K. L., 1990, Analysis of the promoter region of the gene encoding mouse cholesterol side-chain cleavage enzyme, J. Biol. Chem. 265: 11713–11720.

    PubMed  CAS  Google Scholar 

  64. Oonk, R. B., Parker, K. L., Gibson, J. L., and Richards, J. S., 1990, Rat cholesterol side-chain cleavage cytochrome P450 (P450scc) gene. Structure and regulation by cAMP in vitro, J. Bio. Chem. 265: 22392–22401.

    CAS  Google Scholar 

  65. Watanabe, N., Inoue, H., and Fujii-Kuriyama, Y., 1994, Regulatory mechanisms of cAMP-dependent and cell-specific expression of human steroidogenic cytochrome P450scc (CYP11A1) gene, Eur. J. Biochem. 222: 825–834.

    Article  PubMed  CAS  Google Scholar 

  66. Moore, C. C. D., Brentano, S. T., and Miller, W. L., 1990, Human P450scc gene transcription is induced by cyclic AMP and repressed by 12-O-tetradecanoylphorbol-13-acetate and A23187 through independent cis elements, Mol. Cell. Biol. 10: 6013–6023.

    PubMed  CAS  Google Scholar 

  67. Youngblood, G. L., and Payne, A. H., 1992, Isolation and characterization of the mouse P450 17a-hydroxylase/C17–2o-lyase gene (CYP17): Transcriptional regulation of the gene by cyclic adenosine 3’,5’-monophosphate in MA-10 Leydig cells, Mol. Endocrinol. 6: 927–934.

    Article  PubMed  CAS  Google Scholar 

  68. Parissenti, A., Parker, K. L., and Schimmer, B. P., 1993, Identification of promoter elements in the mouse 21-hydroxylase (Cyp21) gene that require a functional cAMP-dependent protein kinase, Mol. Endocrinol. 7: 283–290.

    Article  PubMed  CAS  Google Scholar 

  69. Wilson, T., Mouw, A. R., Weaver, C. A., Millbrandt, J., and Parker, K. L., 1993, The orphan nuclear receptor NGF1-B regulates steroid 21-hydroxylase gene expression, Mol. Cell. Bio. 13: 861–868.

    CAS  Google Scholar 

  70. Watanabe, N., Kitazume, M., Fujisawa, J., Yoshida, M., and Fujii-Kuriyama, Y., 1993, A novel cAMP-dependent regulatory region including a sequence like the cAMP-responsive element, far upstream of the human CYP21A2 gene, Eur..1. Biochem. 214: 521–531.

    Article  PubMed  CAS  Google Scholar 

  71. Waterman, M. R., 1994, Biochemical diversity of cAMP-dependent transcription of steroid hydroxylase genes in the adrenal cortex, J. Biol. Chem. 269: 27783–27786.

    PubMed  CAS  Google Scholar 

  72. Means, G. D., Mahendroo, J., Corbin, C. J., Mathis, J. M., Powell, F. E., Mendelson, C. R., and Simpson, E. R., 1989, Structural analysis of the gene encoding human aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis, J. Biol. Chem. 264: 19385–19391.

    PubMed  CAS  Google Scholar 

  73. Harada, N., Yamada, K., Saito, K., Kibe, N., Dohmae, S., and Takagi, Y., 1990, Structural characterization of the human estrogen synthetase (aromatase) gene, Biochem. Biophys. Res. Commun. 166: 365–372.

    Article  PubMed  CAS  Google Scholar 

  74. Toda, K., Terashima, M., Kamamoto, T., Sumimoto, FI., Yamamoto, Y., Sagara, Y., Ikeda, H., and Shizuta, Y., 1990, Structural and functional characterization of human aromatase P450 gene, Eut: J. Biochem. 193: 559–565.

    Article  CAS  Google Scholar 

  75. Means, G. D., Kilgore, M. W., Mahendroo, M. S., Mendelson, C. R., and Simpson, E. R., 1991, Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues, Mol. Endocrinol. 5: 2005–2013.

    Article  PubMed  CAS  Google Scholar 

  76. Kilgore, M. W., Means, G. D., Mendelson, C. R., and Simpson, E. R., 1992, Alternative promotion of aromatase cytochrome P450 expression in human fetal tissues, Mol. Cell. Endocrinol. 83: R9–R16.

    Article  PubMed  CAS  Google Scholar 

  77. Harada, N., Utsumi, T., and Talcagi, Y., 1993, Tissue-specific expression of the human aromatase cytochrome P450 gene by alternative use of multiple exons I and promoters, and switching of tissue-specific exons I in carcinogenesis, Proc. Natl. Acad. Sci. USA 90: 11312–11316.

    Article  PubMed  CAS  Google Scholar 

  78. Simpson, E. R., Mahendroo, M. S., Means, G. D., Kilgore, M. W., Hinshelwood, M. M., GrahamLorence, S., Amarneh, B., Ito, Y., Fisher, C. R., Michael, M. D., Mendelson, C. R., and Bulun, S. E., 1994, Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis, Endocrine Rev. 15: 342–355.

    CAS  Google Scholar 

  79. Hickey, G. T., Krasnow, J. S., Beattie, W. G., and Richards, J. S., 1990, Aromatase cytochrome P450 in rat ovarian granulosa cells before and after luteini zction: Adenosine 3,5-monophosphate-dependent and independent regulation. Cloning and sequencing of rat aromatase cDNA and 5 genomic DNA, Mol. Endocrinol. 4: 3–12.

    Article  PubMed  CAS  Google Scholar 

  80. Matsumine, H., Herbst, M. A., Ou, S.-H. I., Wilson, J. D., and McPhaul, M. J., 1991, Aromatase mRNA in the extragonadal tissues of chickens with the Henny-feathering trait is derived from a distinct promoter structure that contains a segment of a retroviral long terminal repeat, J. Biol. Chem. 266: 19900–19907.

    PubMed  CAS  Google Scholar 

  81. Mendelson, C. R., Corbin, C. J., Smith, M. E., Smith, J., and Simpson, E. R., 1986, Growth factors suppress, and phorbol esters potentiate the action of dibutyryl cyclic AMP to stimulate aromatase activity of human adipose stromal cells, Endocrinology 118: 968–973.

    Article  PubMed  CAS  Google Scholar 

  82. Evans, C. T., Corbin, C. J., Saunders, C. T., Merrill, J. C., Simpson, E. R., and Mendelson, C. R., 1987, Regulation of estrogen biosynthesis in human adipose stromal cells: Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P450, J. Biol. Chem. 262: 6914–6920.

    PubMed  CAS  Google Scholar 

  83. Toda, K., Miyahara, K., Kawamoto, T., Ikeda, H., Sagara, Y., and Shizuta, Y., 1992, Characterization of a cis-acting regulatory element involved in human aromatase P450 gene expression, Eur. J. Biochem. 205: 303–309.

    Article  PubMed  CAS  Google Scholar 

  84. Fitzpatrick, S. L., and Richards, J. S., 1993, Cis-acting elements of the rat aromatase promoter required for cAMP induction in ovarian granulosa cells and constitutive expression in R2C Leydig cells, Mol. Endocrinol. 7: 341–354.

    Article  PubMed  CAS  Google Scholar 

  85. Usui, E., Noshiro, M., and Okuda, K., 1990, Molecular cloning of cDNA for vitamin D3 25-hydroxylase from rat liver mitochondria, FEBS Lett. 262: 135–138.

    Article  PubMed  CAS  Google Scholar 

  86. Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyereisen, R., Gonzalez, F. J., Coon, M. J., Gunsalus, I. C., Gotoh, O., Okuda, K., and Nebert, D. W., 1993, The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature, DNA Cell Biol. 12: 1–51.

    Article  PubMed  CAS  Google Scholar 

  87. Okuda, K.-I., 1994, Liver mitochondrial P450 involved in cholesterol catabolism and vitamin D activation, J. Lipid Res. 35: 361–372.

    PubMed  CAS  Google Scholar 

  88. Mandel, M. L., Swartz, S. J., and Ghazarian, J. G., 1990, Avian kidney mitochondria] hemeprotein P4501a: Isolation, characterization and NADPH-ferredoxin reductase-dependent activity, Biochim. Biophys. Acta 1034: 239–246.

    Article  PubMed  CAS  Google Scholar 

  89. Hiwatashi, A., Nishii, Y., and Ichikawa, Y., 1982, Purification of cytochrome P4501a (25-hydroxyvitamin D3–1a-hydroxylase) of bovine.kidney mitochondria, Biochem. Biophys. Res. Commun. 105: 320–327.

    Article  PubMed  CAS  Google Scholar 

  90. Gray, R. W., and Ghazarian, J. G., 1989, Solubilization and reconstitution of kidney 25-hydroxyvitamin D3 la-and 24-hydroxylases from vitamin D-replete pigs, Biochem. J 259: 561–568.

    PubMed  CAS  Google Scholar 

  91. Armbrecht, H. J., Nemani, R. K., and Wongsurawat, N., 1993, Regulation of calcium metabolism by the vitamin D hydroxylases, in: Advances in Molecular and Cell Biology (C. R. Jefcoate, ed.) in press.

    Google Scholar 

  92. Ohyama, Y., Noshiro, M., and Okuda, K., 1991, Cloning and expression of cDNA encoding 24-hydroxyvitamin D3 25-hydroxylase, FEBS Lett. 278: 195–198.

    Article  PubMed  CAS  Google Scholar 

  93. Valle, L. D., Belvedere, P., Simontacchi, C., and Colombo, L., 1992, Extraglandular hormonal steroidogenesis in aged rats, J. Steroid Biochem. Mol. Biol. 43: 1095–1098.

    Article  PubMed  Google Scholar 

  94. Nebert, D. W., Nelson, D. R., Coon, M. J., Estabrook, R. W., Feyereisen, R., Fujii-Kuriyama, Y., Gonzalez, F. J., Guengerich, F. P., Gunsalus, I. C., Johnson, E. F., Loper, J. C., Sato, R., Waterman, M. R., and Waxman, D. J., 1991, The P450 superfamily: Update on new sequences, gene mapping, and recommended nomenclature, DNA Cell Biol. 10: 1–14.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kagawa, N., Waterman, M.R. (1995). Regulation of Steroidogenic and Related P450s. In: de Montellano, P.R.O. (eds) Cytochrome P450. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2391-5_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2391-5_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3248-8

  • Online ISBN: 978-1-4757-2391-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics