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Congenital Lipoid Adrenal Hyperplasia

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Book cover Adrenal Disorders

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare disorder, especially in non-Japanese populations, and, hence, some may regard it as a mere medical curiosity. This chapter shows how the curiosity of investigators from Europe, Japan, and the United States led to the solution of this unusual disease, and, in turn, how the solution of this disease provided novel fundamental insights into the regulation of steroid hormone biosynthesis and into developmental endocrinology.

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References

  1. Prader A, Gurtner HP. Das syndrom des pseudohermaphroditismus masculinus bei kongenitaler nebennierenrindenhyperplasie ohne androgenuberproduktion (adrenaler Pseudohermaphroditismus masculinus). Heiv Paed Acta 1955; 10: 397–412.

    CAS  Google Scholar 

  2. Prader A, Siebenmann RE. Nebenniereninsuffizienz bie kongenitaler lipoidhyperplasie der nebennieren. Heiv Paed Acta 1957; 12: 569–595.

    CAS  Google Scholar 

  3. Prader A, Anders CJPA. Zur genetik der kongenitalen lipoidhyperplasie der nebennieren. Heiv Paed Acta 1962; 17: 285–289.

    CAS  Google Scholar 

  4. Tilp A. Hochgradige Verfettung der nebenniere eines sauglings. Verhandlungen der deutschensch gesellschaft fur pathologie 1913; 16: 305–307.

    Google Scholar 

  5. Brutschy P. Hochgradige lipoidhyperplasie beider nebennieren mit herdformigen kalkablagerunger bei einem fall von hypospadiasis penisscrotalis und doppelseitigem kryptorchismus mit unechter akzessorisher nebenniere am rechten hoden (pseudohermaphroditismus masculinus externus). Frankfurter Zeitschriff für Pathologie 1920; 24: 203–240

    Google Scholar 

  6. Sandison AT. A form of lipoidosis of the adrenal cortex in an infant. Arch Dis Childh 1955; 30: 538–541.

    Article  PubMed  CAS  Google Scholar 

  7. Zahn J. Ueber intersexualitat und nebennierenhyperplasie. Schweizerische Medizinische Wochenschrift 1948; 78: 480–486.

    PubMed  CAS  Google Scholar 

  8. Camacho AM, Kowarski A, Migeon CJ, Brough A. Congenital adrenal hyperplasia due to a deficiency of one of the enzymes involved in the biosynthesis of pregnenolone. J Clin Endocrinol Metab 1968; 28: 153–161.

    Article  PubMed  CAS  Google Scholar 

  9. Degenhart HJ, Visser KHA, Boon H, O’Doherty NJD. Evidence for deficiency of 20a cholesterol hydroxylase activity in adrenal tissue of a patient with lipoid adrenal hyperplasia. Acta Endocrinol 1972; 71: 512–518.

    PubMed  CAS  Google Scholar 

  10. Lin D, Sugawara T, Strauss JF III, Clark BJ, Stocco DM, Saenger P, et al. Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 1995; 267: 1828–1831.

    Article  PubMed  CAS  Google Scholar 

  11. Koizumi S, Kyoya S, Miyawaki T, Kidani H, Funabashi T, Nakashima H, et al. Cholesterol side-chain cleavage enzyme activity and cytochrome P450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease). Clin Chem Acta 1977; 77: 301–306.

    Article  CAS  Google Scholar 

  12. Omura T, Sato R, Cooper DY, Rosenthal O, Estabrook RW. Function of cytochrome P450 of microsomes. Fed Proc 1965; 24: 1181–1189.

    PubMed  CAS  Google Scholar 

  13. Shikita M, Hall PF. Cytochrome P-450 from bovine adrenocortical mitochondria: an enzyme for the side chain cleavage of cholesterol. I. Purification and properties. J Biol Chem 1973; 248: 5596–5604.

    Google Scholar 

  14. Miller WL. Molecular biology of steroid hormone synthesis. Endocr Rev 1988; 9: 295–318.

    Article  PubMed  CAS  Google Scholar 

  15. Hauffa BP, Miller WL, Grumbach MM, Conte FA, Kaplan SL. Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20,22 desmolase) in a patient treated for 18 years. Clin Endocrinol 1985; 23: 481–493.

    Article  CAS  Google Scholar 

  16. Matteson KJ, Chung B, Urdea MS, Miller WL. Study of cholesterol side chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc oligodeoxyribonucleotide probes. Endocrinology 1986; 118: 1296–1305.

    Article  PubMed  CAS  Google Scholar 

  17. Chung B, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc Natl Acad Sci USA 1986; 83: 8962–8966.

    Article  PubMed  CAS  Google Scholar 

  18. Morohashi K, Sogawa K, Omura T, Fujii-Kuriyama Y. Gene structure of human cytochrome P-450(scc), cholesterol desmolase. J Biochem 1987; 101: 879–887.

    PubMed  CAS  Google Scholar 

  19. Lin D, Gitelman SE, Saenger P, Miller WL. Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia. J Clin Invest 1991; 88: 1955–1962.

    Article  PubMed  CAS  Google Scholar 

  20. Stocco DM, Clark BJ. Regulation of the acute production of steroids in steroidogenic cells. Endocr Rev 1996; 17: 221–244.

    PubMed  CAS  Google Scholar 

  21. Stone D, Hechter O. Studies on ACTH action in perfused bovine adrenals: aspects of progesterone as an intermediary in cortico-steroidogenesis. Arch Biochem Biophys 1955; 54: 121–128.

    Article  PubMed  CAS  Google Scholar 

  22. Ferguson JJ. Protein synthesis and adrenocorticotropin responsiveness. J Biol Chem 1963; 238: 2754 2759.

    Google Scholar 

  23. Garren LD, Ney RL, Davis WW. Studies on the role of protein synthesis in the regulation of corticosterone production by adrenocorticotropic hormone in vivo. Proc Natl Acad Sci USA 1965; 53: 1443–1450.

    Article  PubMed  CAS  Google Scholar 

  24. Garren LD, Davis WW, Crocco RM. Puromycin analogs: action of adrenocorticotropic hormone and the role of glycogen. Science 1966; 152: 1386–1388.

    Article  PubMed  CAS  Google Scholar 

  25. Waterman MR, Simpson ER. Regulation of steroid hydroxylase gene expression is multifactorial in nature. Recent Prog Horm Res 1989; 45: 533–566.

    PubMed  CAS  Google Scholar 

  26. Moore CCD, Miller WL. The role of transcriptional regulation in steroid hormone biosynthesis. J Steroid Biochem Mol Biol 1991; 40: 517–525.

    Article  PubMed  CAS  Google Scholar 

  27. Golos TJ, Miller WL, Strauss JF III. Human chorionic gonadotropin and 8-bromo-cyclic adenosine mono phosphate promote an acute increase in cytochrome P450scc and adrenodoxin messenger RNAs in cultured human granulosa cells by a cycloheximide-insensitive mechanism. J Clin Invest 1987; 80: 896–899.

    Article  PubMed  CAS  Google Scholar 

  28. Picado-Leonard J, Voutilainen R, Kao L, Chung B, Strauss JF III, Miller WL. Human adrenodoxin: Cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells. J Biol Chem 1988; 263:32403244, corrected 11, 016.

    Google Scholar 

  29. Ringler GE, Kao L-C, Miller WL, Strauss JF III. Effects of 8-bromo-cAMP on expression of endocrine functions by cultured human trophoblast cells. Regulation of specific mRNAs. Mol Cell Endocrinol 1989; 62: 13–21.

    Article  Google Scholar 

  30. Mellon SH, Vaisse C. cAMP regulates P450scc gene expression by a cycloheximide-insensitive mechanism in cultured mouse leydig MA-10 cells. Proc Natl Acad Sci USA 1989; 86: 7775–7779.

    Article  PubMed  CAS  Google Scholar 

  31. Chandebhan R, Noland BJ, Scallen TJ, Vahouny GV. Sterol carrier protein 2: Delivery of cholesterol from adrenal lipid droplets to mitochondria for pregnenolone synthesis. J Biol Chem 1982; 257: 8928–8934.

    Google Scholar 

  32. Vahouny GV, Chanderbhan R, Noland BJ, Irwin D, Dennis P, Labmeth JD, et al. Sterol carrier protein identification of adrenal sterol carrier protein 2 and site of action for mitochondrial cholesterol utilization. J Biol Chem 1983; 258:11,731–11,737.

    Google Scholar 

  33. Pedersen RC, Brownie AC. Cholesterol side-chain cleavage in the rat adrenal cortex: Isolation of a cycloheximide-sensitive activator peptide. Proc Natl Acad Sci USA 1983; 80: 1882–1886.

    Article  PubMed  CAS  Google Scholar 

  34. Pedersen RC, Brownie AC. Steroidogenesis activator polypeptide isolated from a rat Leydig cell tumor. Science 1987; 236: 188–190.

    Article  PubMed  CAS  Google Scholar 

  35. Li X, Warren DW, Gregorie J, Pedersen RC, Lee AS. The rat 78000 dalton glucose regulated protein (GRP-78) as a precursor for the rat steroidogenesis activator polypeptide (SAP): the SAP coding sequence is homologous with the terminal end of GRP-78. Mol Endocrinol 1989; 3: 1944–1952.

    Article  PubMed  CAS  Google Scholar 

  36. Iida S, Papadopoulos V, Hall PF. The influence of exogenous free cholesterol on steroid synthesis in cultured adrenal cells. Endocrinology 1989; 124: 2619–2624.

    Article  PubMed  CAS  Google Scholar 

  37. Papadopoulos V. Peripheral-type benzodiazepine/diazepam binding inhibitor receptor. Biological role in steroidogenic cell function. Endocr Rev 1993; 14: 222–240.

    PubMed  CAS  Google Scholar 

  38. Yanagibashi K, Ohno Y, Kawamura M, Hall PF. The regulation of intracellular transport of cholesterol in bovine adrenal cells: purification of a novel protein. Endocrinology 1988; 123: 2075–2082.

    Article  PubMed  CAS  Google Scholar 

  39. Besman MJ, Yanagibashi K, Lee TD, Kawamura M, Hall PF, Shively JE. Identification of des(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor. Proc Natl Acad Sci USA 1989; 86: 4897–4901.

    Article  PubMed  CAS  Google Scholar 

  40. Papadopoulos V, Amri H, Boujrad N, Cascio C, Culty M, Gamier M, et al. Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis. Steroids 1997; 62: 21–28.

    Article  PubMed  CAS  Google Scholar 

  41. Lin D, Chang YJ, Strauss JF III, Miller WL. The human peripheral benzodiazepine receptor gene. Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia. Genomics 1993; 18: 643–650.

    Article  PubMed  CAS  Google Scholar 

  42. Pon LA, Orme-Johnson NR. Acute stimulation of steroidogenesis in corpus luteum and adrenal cortex by peptide hormones. J Biol Chem 1986; 261: 6594–6599.

    PubMed  CAS  Google Scholar 

  43. Stocco DM, Sodeman TC. The 30 kDa mitochondrial protein induced by hormone stimulation in MA-10 mouse Leydig tumor cells are processed from larger precursors. J Biol Chem 1991; 266:19, 73119, 738.

    Google Scholar 

  44. Epstein LF, Orme-Johnson NR. Regulation of steroid hormone biosynthesis. Identification of precursors of a phosphoprotein targeted to the mitochondrion in stimulated rat adrenal cortex cells. J Biol Chem 1991; 266:19, 739–19, 745.

    Google Scholar 

  45. Clark BJ, Wells J, King SR, Stocco DM. The purification, cloning and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 cells mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem 1994; 269:28, 314–28, 322.

    Google Scholar 

  46. Saenger P, Klonari Z, Black SM, Compagnone N, Mellon SH, Fleischer A, et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab 1995; 80: 200–205.

    Article  PubMed  CAS  Google Scholar 

  47. Sugawara T, Holt JA, Driscoll D, Strauss JF III, Lin D, Miller WL, et al. Human steroidogenic acute regulatory protein (StAR): Functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and an expressed pseudogene to chromosome 13. Proc Natl Acad Sci USA 1995; 92: 4778–4782.

    Article  PubMed  CAS  Google Scholar 

  48. Tee MK, Lin D, Sugawara T, Holt JA, Guiguen Y, Buckingham B, et al. T -4 A transversion 11 bp from a splice acceptor site in the gene for steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia. Hum Mol Genet 1995; 4: 2299–2305.

    Article  PubMed  CAS  Google Scholar 

  49. Toaff ME, Schleyer H, Strauss JF III. Metabolism of 25-hydroxycholesterol by rat luteal mitochondria and dispersed cells. Endocrinology 1982; 111: 1785–1790.

    Article  PubMed  CAS  Google Scholar 

  50. Harikrishna JA, Black SM, Szklarz GD, Miller WL. Construction and function of fusion enzymes of the human cytochrome P450scc system. DNA Cell Biol 1993; 12: 371–379.

    Article  PubMed  CAS  Google Scholar 

  51. Bose HS, Sugawara T, Strauss JF III, Miller WL. The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. N Engl J Med 1996; 335: 1870–1878.

    Article  PubMed  CAS  Google Scholar 

  52. Kirkland RT, Kirkland JL, Johnson CM, Horning MG, Librik L, Clayton GW. Congenital lipoid adrenal hyperplasia in an eight-year-old phenotypic female. J Clin Endocrinol Metab 1973; 36: 488–496.

    Article  PubMed  CAS  Google Scholar 

  53. Matsuo N, Tsuzaki S, Anzo M, Ogata T, Sato S. The phenotypic definition of congenital lipoid adrenal hyperplasia: analysis of the 67 Japanese patients (abstract). Horm Res 41 1994; (suppl): 106 (abstract)

    Google Scholar 

  54. Zuber MX, Mason JI, Simpson ER, Waterman MR. Simultaneous transfection of COS-1 cells with mitochondrial and microsomal steroid hydroxylases: incorporation of a steroidogenic pathway into non-steroidogenic cells. Proc Natl Acad Sci USA 1988; 85: 699–703.

    Article  PubMed  CAS  Google Scholar 

  55. Miller WL. Mitochondria’ specificity of the early steps in steroidogenesis. J Steroid Biochem Mol Biol 1995; 55: 607–616.

    Article  PubMed  CAS  Google Scholar 

  56. Brentano ST, Black SM, Lin D, Miller WL. cAMP post-transcriptionally diminishes the abundance of adrenodoxin reductase mRNA. Proc Natl Acad Sci USA 1992; 89: 4099–4103.

    Article  PubMed  CAS  Google Scholar 

  57. Sugawara T, Lin D, Holt JA, Martin KO, Javitt NB, Miller WL, et al. The structure of the human steroidogenic acute regulatory (StAR) protein gene: StAR stimulates mitochondria) cholesterol 27hydroxylase activity. Biochemistry 1995b; 34:12, 506–12, 512.

    Google Scholar 

  58. Mellon SH. Neurosteroids: biochemistry, modes of action, and clinical relevance. J Clin Endocrinol Metab 1994; 78: 1003–1008.

    Article  PubMed  CAS  Google Scholar 

  59. Bose HS, Pescovitz OH, Miller WL. Spontaneous feminization in a 46, XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein. J Clin Endocrinol Metab 1997.

    Google Scholar 

  60. Mesiano S, Coulter CL, Jaffe RB. Localization of cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17a-hydroxylase/17,20 lyase, and 3(3-hydroxysteroid dehydrogenase-isomerase steroidogenic enzymes in human and rhesus monkey fetal adrenal glands: reappraisal of functional zonation. J Clin Endocrinol Metab 1993; 77: 1184–1189.

    Article  PubMed  CAS  Google Scholar 

  61. Voutilainen R, Miller WL. Developmental expression of genes for the steroidogenic enzymes P450scc (20,22 desmolase), P450c17 (17a-hydroxylase/17,20 lyase) and P450c21 (21-hydroxylase) in the human fetus. J Clin Endocrinol Metab 1986; 63: 1145–1150.

    Article  PubMed  CAS  Google Scholar 

  62. Grumbach MM, Styne DM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: Wilson JD and Foster DW, eds. Williams Textbook of Endocrinology, 8th Ed, WB Saunders, Philadelphia, PA, 1992, pp. 1139–1221.

    Google Scholar 

  63. Zanaria E, Muscatelli F, Bardom B, Strom TM, Guioli S, Guo W, et al. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature 1994; 372: 635–641.

    Article  PubMed  CAS  Google Scholar 

  64. Guo W, Burris TP, McCabe ERB. Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/ gonadal axis. Biochem Mol Med 1994; 56: 8–13.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  66. Arakane F, Sugawara T, Nishino H, Liu Z, Holt JA, Pain D, et al. Steroidogenic acute regulatory protein (StAR) retains activity in the absence of its mitochondria) targeting sequence: implications for the mechanism of StAR action. Proc Natl Acad Sci USA 1996; 93:13, 731–13, 736.

    Google Scholar 

  67. Fujieda K, Tajima T, Nakae J, Sugawara T, Strauss JF III. Molecular analysis of the steroidogenic acute regulatory protein (StAR) gene from 23 Japanese patients with congenital lipoid adrenal hyperplasia. 10th Int Cong Endocrinol, Program and Abstr Vol 1 San Francisco, CA, (Abs #P2–728), 1996, p 586.

    Google Scholar 

  68. Hall PF. The roles of calmodulin, actin and vimentin in steroid synthesis by adrenal cells. Steroids 1997; 62: 185–189.

    Article  PubMed  CAS  Google Scholar 

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Miller, W.L. (2001). Congenital Lipoid Adrenal Hyperplasia. In: Margioris, A.N., Chrousos, G.P. (eds) Adrenal Disorders. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-101-5_22

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  • DOI: https://doi.org/10.1007/978-1-59259-101-5_22

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-029-8

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