Abstract
The adrenal cortex produces three principal categories of steroid hormones that regulate a wide variety of physiologic processes from fetal to adult life. Mineralocorticoids, principally aldosterone, regulate renal sodium retention and thus profoundly influence electrolyte balance, intravascular volume, and blood pressure. Glucocorticoids, principally Cortisol, are named for their carbohydrate-mobilizing activity, but are ubiquitous physiologic regulators influencing a wide variety of bodily functions. Adrenal androgens serve no essential physiologic role, but do mediate some secondary sexual characteristics in females, and their overproduction may result in virilism. These biologically active steroids are synthesized from cholesterol by the complex series of enzymatic conversions summarized in Fig. 1. The molecular biology of steroid hormone synthesis has been reviewed in detail recently (Miller, 1988a; Strauss and Miller, 1990), and thus is only outlined briefly here. Genetic disorders exist for each of the steps in steroid hormone synthesis. To understand the phenotypic, clinical manifestations of each of these disorders it is important to understand the steroidogenic pathways and the enzymes that mediate steroid hormone synthesis.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Al-Othman, A. N., Docherty, K., Makgoba, M. W., Sheppard, M. C., and London, D. R., 1988, DNA and RNA analysis of cytochrome P-450 21-hydroxylase: Transcriptional activity in congenital adrenal hyperplasia, J. Mol. Endocrinol. 1: 157–164.
Amor, M., Tosi, M., Duponchel, C., Steinmetz, M., and Meo, T., 1985, Liver cDNA probes disclose two cytochrome P450 genes duplicated in tandem with the complement C4 loci of the mouse H-2S region, Proc. Natl. Acad. Sci. USA 82: 4453–4457.
Amor, M., Parker, K. L., Globerman, H., New, M. I., and White, P. C., 1988, Mutation in the CYP21B gene (Ile-172-Asn) causes steroid 21-hydroxylase deficiency, Proc. Natl. Acad. Sci. USA 85: 1600–1604.
Aston, C. E., Sherman, S. L., Morton, N. E., Speiser, P. W., and New, M. I., 1988, Genetic mapping of the 21-hydroxylase locus: Estimation of small recombination frequencies, Am. J. Hum. Genet. 43: 304–310.
Baltimore, D., 1981, Gene conversion: Some implications for immunoglobulin genes, Cell 24: 592–594.
Baron, J., Taylor, W. E., and Masters, B. S. S., 1972, Immunochemical studies on electron chains involving cytochrome P450. The role of the iron-sulfur protein, adrenodoxin in mixed function oxidation reactions, Arch. Biochem. Biophys. 150: 105–115.
Belt, K. T., Carroll, M. C., and Porter, R. R., 1984, The structural basis of the multiple forms of human complement component C4, Cell 36: 907–914.
Besman, M. J., Yanagibashi, K., Lee, T. D., Kawamura, M., Hall, P. F., and Shively, J. E., 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 86: 4897–4901.
Black, S. D., and Coon, M. J., 1987, P-450 cytochromes: Structure and function, Adv. Enzymol. Relat. Areas Mol. Biol 60: 35–87.
Brentano, S. T., Picado-Leonard, J., Mellon, S. H., Moore, C. C. D., and Miller, W. L., Tissue-specific, cAMP-induced, and phorbol ester repressed expression from the human P450cl7 promoter in mouse cells, Mol. Endocrinol. 4: 1972–1979.
Bristow, J., Gitelman, S. E., Shi, Y., and Miller, W. L., 1990, Structure of the gene overlapping the P450c21B gene suggests it encodes a tissue-specific extracellular matrix protein, Pediatr. Res. 27:76A, Abstract 419.
Brown, M. S., Kovanen, P. T., and Goldstein, J. L., 1979, Receptor-mediated uptake of lipoprotein-cholesterol and its utilization for steroid synthesis in the adrenal cortex, Rec. Prog. Horm. Res. 35: 215–257.
Cara, J. F., Moshang, T., Jr., Bongiovanni, A. M., and Marx, B. S., 1985, Elevated 17-hydroxyprogesterone and testosterone in a newborn with 3-beta-hydroxysteroid dehydrogenase deficiency, N. Engl. J. Med. 313: 618–621.
Carroll, M. C., Campbell, R. D., Bentley, D. R., and Porter, R. R., 1984, A molecular map of the human major histocompatibility class III region lining complement genes C4, C2 and factor B, Nature 307: 237–241.
Carroll, M. C., Campbell, R. D., and Porter, R. R., 1985a, Mapping of steroid 21-hydroxylase genes to complement component C4 genes in HLA, the major histocompatibility locus in man, Proc. Natl. Acad. Sci. USA 82: 521–525.
Carroll, M. C., Palsdottir, A., Belt, K. T., and Porter, R. R., 19856, Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region, EMBO J. 4: 2547–2552.
Casey, M. L., and MacDonald, P. C., 1982, Extraadrenal formation of a mineralocorticoid: Deoxycorticosterone and deoxycorticosterone sulfate biosynthesis and metabolism, Endocr. Rev. 3: 396–403.
Casey, M. L., Winkel, C. A., and MacDonald, P. C., 1983, Conversion of progesterone to deoxycorticosterone in the human fetus: Steroid 21-hydroxylase activity in fetal tissues, J. Steroid Biochem. 18: 449–452.
Chanderbhan, R., Noland, B. J., Scallen, T. J., Vahouny, G. V., 1982, Sterol carrier protein 2: Delivery of cholesterol from adrenal lipid droplets to mitochondria for pregnenolone synthesis, J. Biol. Chem. 257: 8928–8934.
Chang, C. Y., Wu, D. A., Lai, C. C., Miller, W. L., and Chung, B., 1988, Cloning and structure of the human adrenodoxin gene, DNA 7: 609–615.
Chang, C. Y., Wu, D. A., Mohandas, T. K., and Chung, B., 1990, Structure, sequence, chromosomal location, and evolution of the human ferredoxin gene family, DNA Cell Biol. 9: 205–212.
Chaplin, D. D., Galbreath, L. G., Seidman, J. G., White, P. C., and Parker, K. L., 1986, Nucleotide sequence analysis of murine 21-hydroxylase genes: Mutations affecting gene expression, Proc. Natl. Acad. Sci. USA 83: 9601–9605.
Chetkowski, R. J., DeFazio, J., Shamonki, I., Judd, H. L., and Chang, R. J., 1984, The incidence of the late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency among hirsute women, J. Clin. Endocrinol. Metab. 58: 595–598.
Chiou, S. H., Hu, M. C., and Chung, B.-C., 1990, A missense mutation of lie 172Asn or Arg356Trp causes steroid 21-hydroxylase deficiency, J. Biol. Chem. 265: 3549–3552.
Chrousos, G. P., Loriaux, D. L., Mann, D. L., and Cutler, G. B., 1982, Late-onset 21-hydroxylase deficiency mimicking idiopathic hirsutism or polycystic ovarian disease: An allelic variant of congenital virilizing adrenal hyperplasia with a milder enzymatic defect, Ann. Intern. Med. 96: 143–148.
Chua, S. C., Szabo, P., Vitek, A., Grzeschik, K.-H., John, M., and White, P. C., 1987, Cloning of cDNA encoding steroid 110-hydroxylase, P450cll, Proc. Natl. Acad. Sci. USA 84: 7193–7197.
Chung, B., Matteson, K. J., and Miller, W. L., 1985, Cloning and characterization of the bovine gene for steroid 21-hydroxylase (P450c21), DNA 4: 211–219.
Chung, B., Matteson, K. J., and Miller, W. L., 1986a, Structure of a bovine gene for P450c21 (steroid 21-hydroxylase) defines a new cytochrome P450 gene family, Proc. Natl. Acad. Sci. USA 83: 4243–4247.
Chung, B., Matteson, K. J., Voutilainen, R., Mohandas, T. K., and Miller, W. L., 19866, 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 83: 8962–8966.
Chung, B., Picado-Leonard, J., Haniu, M., Bienkowski, M., Hall, P. F., Shively, J. E., and Miller, W. L., 1987, Cytochrome P450cl7 (steroid 17a-hydroxylase/17,20 lyase): Cloning of human adrenal and testis cDNAs indicate the same gene is expressed in both tissues, Proc. Natl. Acad. Sci. USA 84: 407–411.
Collier, S., Sinnott, P. J., Dyer, P. A., Price, D. A., Harris, R., and Strachan, T., 1989, Pulse field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement C4 gene repeats in 21-hydroxylase deficiency haplotypes, EMBO J. 8: 1393–1402.
Conneely, O. M., Headon, D. R., Olson, C. D., Ungar, F., and Dempsey, M. E., 1984, Intra-mitochondrial movement of adrenal sterol carrier protein with cholesterol in response to corticotropin, Proc. Natl. Acad. Sci. USA 260: 4733–4739.
Davidson, J. A., Kippax, R. L., and Dyer, P. A., 1988, A study of HLA-A, B, DR and Bf bearing haplotypes derived from 304 families resident in the northwest of England, J. Immunogenet. 18: 227–237.
Dawkins, R. L., Martin, E., Kay, P. H., Garlepp, M. J., Wilton, A. N., and Stuckey, M. S., 1987, Heterogeneity of steroid 21-hydroxylase genes in classical congenital adrenal hyperplasia, J. Immunogenet. 14: 89–98.
DiBlasio, A. M., Voutilainen, R., Jaffe, R. B., and Miller, W. L., 1987, Hormonal regulation of mRNAs for P450scc (cholesterol side-chain cleavage enzyme) and P450cl7 (17a- hydroxylase/17,20 lyase) in cultured human fetal adrenal cells, J. Clin. Endocrinol. Metab. 65: 170–175.
Donohoue, P. A., Van Dop, C., McLean, R. H., White, P. C., Jospe, N., and Migeon, C. J., 1986, Gene conversion in salt-losing congenital adrenal hyperplasia with absent complement C4B protein, J. Clin. Endocrinol. Metab. 62: 995–1002.
Donohoue, P. A., Jospe, N., Migeon, C. J., and VanDop, C., 1989, Two distinct areas of unequal crossing over within the steroid 21-hydroxylase genes produce absence of CYP21B, Genomics 5: 397–406.
Donohoue, P. A., Neto, R. S., Collins, M. M., and Migeon, C. J., 1990, Nco I restriction site within CYP21B (steroid 21-hydroxylase) is a normal polymorphism, Mol. Endocrinol. 4: 1354–1362.
Dumic, M., Brkljacic, L., Speiser, P. W., Wood, E., Crawford, C., Plavsic, V., Baniceviac, M., Radmanovic, S., Radica, A., Kasteian, A., and New, M. I., 1990, An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population, Acta Endocrinol 122: 703–710.
Dunham, I., Sargent, C. A., Trowsdale, J., and Campbell, R. D., 1987, Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis, Proc. Natl. Acad. Sci. USA 84: 7237–7241.
Dunham, I., Sargent, C. A., Dawkins, R. L., and Campbell, R. D., 1989, Direct observation of the gene organization of the complement C4 and 21-hydroxylase loci by pulse field gel electrophoresis, J. Exp. Med. 169: 1803–1816.
Dupont, B., Oberfield, S. E., Smithwick, E. R., Lee, T. D., and Levine, L. S., 1977, Close genetic linkage between HLA and congenital adrenal hyperplasia (21-hydroxylase deficiency), Lancet ii:1309–1312.
Dupont, B., Pollack, M. S., Levine, L. S., O’Neill, G. J., Hawkins, B. R., and New, M. I., 1981, Congenital adrenal hyperplasia: Joint report from the eighth international histocompatibility workshop, in: Histocompatibility Testing 1980 ( P. I. Terasaki, ed.), Springer-Verlag, Berlin, pp. 693–706.
Duque, C., Morisaki, M., Ikekawa, N., and Shikita, M., 1978, The enzyme activity in bovine adrenal cortical cytochrome P450 produces pregnenolone from cholesterol: Kinetic and electrophoretic studies on the reactivity of hydroxycholesterol intermediates, Biochem. Biophys. Res. Commun. 82: 174–178.
Egel, R., 1981, Intergenic conversion and reiterated genes, Nature 290: 191–192.
Ehlen, T., and Dubeau, L., 1989, Detection of Ras point mutations by polymerase chain reaction using mutation-specific, inosine-containing oligonucleotide primers, Biochem. Biophys. Res. Commun. 160: 441–447.
Fiet, J., Gueux, B., Gourmelen, M., Kuttenn, F., Vexiau, P., Cuillin, P., Pham-Huu-Trung, M.-T., Vilette, J.-M., Rauz-Demay, M.-C., Galons, H., and Julien, R., 1988, Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17- hydroprogesterone values as biological markers of late-onset adrenal hyperplasia, J. Clin. Endocrinol. Metab. 66: 659–667.
Fincham, J. R. S., and Oliver, P., 1989, Initiation of recombination, Nature 338: 14–15.
Fleischnick, E., Awdeh, Z. L., Raum, D., Granados, J., Alosco, S. M., Crigler, J. R., Jr., Gerald, P. S., Giles, C. M., Ynis, E. J., and Alper, C. A., 1983, Extended MHC haplotypes in 21-hydroxylase deficiency congenital adrenal hyperplasia: Shared genotypes in unrelated patients, Lancet i: 152–156.
Forest, M. G., Betuel, H., Couillin, P., and Boue, A., 1981, Prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency by steroid analysis in the amniotic fluid of mid-pregnancy: Comparison with HLA typing in 17 pregnancies at risk for CAH, Prena. Diagn. 1: 197–207.
Forest, M. G., Betuel, H., and David, M., 1989, Prenatal treatment in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Update 88 of the French multicentric study, Endocr. Res. 15: 277–301.
Frasier, S. D., Thorneycroft, I. H., Weiss, B. A., and Horton, R., 1975, Elevated amniotic fluid concentration of 17a-hydroxyprogesterone in congenital adrenal hyperplasia, Pediatr. 86: 310–314.
Garlepp, M. J., Wilton, A. N., Dawkins, R. L., and White, P. C., 1986, Rearrangement of 21-hydroxylase genes in disease-associated MHC supratypes, Immunogenetics 23: 100–105.
Geffrotin, C., Chardon, P., DeAndres-Cara, D. F., Feil, R., Renard, C., and Vaiman, M., 1990, The swine steroid 21-hydroxylase gene (CYP21): Cloning and mapping within the swine leukocyte antigen locus, Anim. Genet. 21: 1–13.
Giles, C., Uring-Lambert, B., Boksch, W., Braun, M., Goetz, J., Neumann, R., Mauff, G., and Hauptman, G., 1987, The study of a French family with two duplicated C4A haplotypes, Hum. Genet. 77: 359–365.
Gitelman, S. E., Bristow, J., Shi, Y., and Miller, W. L., 1990, Structure and possible function of a gene overlapping the P450c21A pseudogene, Pediatr. Res. 27:76A, Abstract 441.
Globerman, H., Amor, M., Parker, P. L., New, M. I., and White, P. C., 1988, Nonsense mutation causing steroid 21-hydroxylase deficiency, J. Clin. Invest. 82: 139–144.
Gnanaiah, W., and Omdahl, J. L., 1986, Isolation and characterization of pig kidney mitochondrial ferredoxin: NADP+ oxidoreductase, J. Biol. Chem. 261: 12649–12654.
Goebelsmann, U., Zachmann, M., Davajan, V., Israel, R., Mestman, J. H., and Mishell, D. R., 1976, Male pseudohermaphroditism consistent with 17,20-desmolase deficiency, Gynecol. Invest. 7: 138–156.
Golos, T. G., and Strauss, J. F., Ill, 1988, 8-bromo adenosine cyclic 3′5′ phosphate rapidly increases 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in human granulosa cells: Role of cellular sterol balance in controlling the response to tropic stimulation, Biochemistry 27: 3503–3506.
Golos, T. G., Soto, E. A., Tureck, R. W., and Strauss, J. F., Ill, 1985, Human chorionic gonadotropin and 8-bromoadenosine 3′5′-monophosphate stimulate [1251] low density lipoprotein uptake and metabolism by luteinized human granulosa cells in culture, J. Clin. Endocrinol. Metab. 61: 633–638.
Gonzalez, F. J., 1989, The molecular biology of cytochrome P450s, Pharmacol. Rev. 40: 243–288.
Gourmelen, M., Gueux, B., Pham-Huu-Trung, M. T., Fiet, J., Raux-Demay, M. C., and Girard, F., 1987, Detection of heterozygous carriers for 21-hydroxylase deficiency by plasma 21-deoxycortisol measurement, Acta Endocrinol. 116: 507–512.
Gwynne, J. T., and Strauss, J. F., Ill, 1982, The role of lipoproteins in steroidogenesis and cholesterol metabolism in steroidogenic glands, Endocr. Rev. 3: 299–329.
Haglund-Stengler, B., Ritzen, E. M., and Luthman, H., 1990, 21-hydroxylase deficiency- Disease causing mutations categorized by densitometry of 21-hydroxylase-specific doxyribonucledic acid fragments, J. Clin. Endocrinol. Metab. 70: 43–48.
Hanukoglu, I., and Jefcoate, C. R., 1980, Mitochondrial cytochrome P-450scc: Mechanism of electron transport by adrenodoxin, J. Biol. Chem. 255: 3057–3061.
Harada, F., Kimura, A., Iwanaga, T., Shimozawa, K., Yata, J., and Sasazuki, T., 1987, Gene conversion-like events cause steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia, Proc. Natl. Acad. Sci. USA 84: 8091–8094.
Hauffa, B. P., Miller, W. L., Grumbach, M. M., Conte, F. A., and Kaplan, S. L., 1985, Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20,22 desmolase) in a patient treated for 18 years, Clin. Endocrinol. 23: 481–493.
Hauptmann, G., Tappeiner, G., and Schifferli, J. A., 1988, Inherited deficiency of the fourth component of human complement, Immunodeficiency Rev. 1: 3–22.
Higashi, Y., Yoshioka, H., Yamane, M., Gotoh, O., and Fujii-Kuriyama, Y., 1986, Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: A pseudogene and a genuine gene, Proc. Natl. Acad. Sci. USA 83: 2841–2845.
Higashi, Y., Tanae, A., Inoue, H., and Fujii-Kuriyama, Y., 1988a, Evidence for frequent gene conversions in the steroid 21-hydroxylase (P-450c21) gene: Implications for steroid 21-hydroxylase deficiency, Am. J. Hum. Genet. 42: 17–25.
Higashi, Y., Tanae, A., Inoue, Y., Hiroshima, T., Fujii-Kuriyama, Y., 1988b, Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: Possible gene conversion products, Proc. Natl. Acad. Sci. USA 85: 7486–7490.
Higashi, Y., Hiromasa, T., Tanae, A., Miki, T., Nakura, J., Kondo, T., Ohura, T., Ogawa, E., Nagayama, K., and Fujii-Kuriyama, Y., 1991, Effects of individual mutations in the P-450c21 pseudogene on P-450c21 activity and their distribution in patient genomes of congenital steroid 21-hydroxylase deficiency, J. Biochem. (Tokyo) 109: 638–644.
Holler, W., Scholz, S., Knorr, D., Bidlingmaier, F., Keller, E., and Ekkehard, D. A., 1985, Genetic differences between the salt-wasting, simple virilizing and nonclassical types of congenital adrenal hyperplasia, J. Clin. Endocrinol. Metab. 60: 757–763.
Hood, L., Campbell, J. H., and Elgin, S. C. R., 1975, The organization expression and evolution of antibody genes and other multigene families, Annu. Rev. Genet. 9: 305–353.
Hu, M. C., and Chung, B.-C., 1990, Expression of human 21-hydroxylase (P450c21) in bacterial and mammalian cell—A system to characterize normal and mutant enzymes, Mol. Endocrinol. 4: 893–898.
Hughes, I. A., Dyas, J., Riad-Fahmy, D., and Laurence, K. M., 1987, Prenatal diagnosis of congenital adrenal hyperplasia: Reliability of amniotic fluid steroid analysis, J. Med. Genet. 24: 344–347.
Jackson, J. A., and Fink, G. R., 1981, Gene conversion between duplicated elements in yeast, Nature 292: 306–311.
Jefcoate, C. R., McNamara, B. C., and DiBartolomeis, M. S., 1986, Control of steroid synthesis in adrenal fasciculata, Endocr. Res. 12: 315–350.
Jospe, N., Donohoue, P. A., Van Dop, C., McLean, R. H., Bias, W., and Migeon, C. J., 1987, Prevalence of polymorphic 21-hydroxylase gene (CAH21B) mutations in salt- losing congenital adrenal hyperplasia, Biochem. Biophys. Res. Commun. 142: 798–804.
Kay, P. H., Dawkins, R. L., Bowling, A. T., and Bernoco, D., 1987, Heterogeneity and linkage of equine C4 and steroid 21-hydroxylase genes, J. Immunogenet. 14: 247–253.
Kimura, T., 1981, ACTH stimulation on cholesterol side chain cleavage activity of adrenocortical mitochondria, Mol. Cell. Biochem. 36: 105–122.
Kochhan, L., Janssen, S., Knorr, D., Olek, K., and Bidingmaier, R., 1990, HLA class- I-hydroxylase, complement C4-hydroxylase and 21-hydroxylase probes in the genetic analysis of 21-hydroxylase deficiency, J. Clin. Chem. Clin. Biochem. 28: 413–417.
Kohn, B., Levine, L. S., Pollack, M. S., Pang, S., Lorenzen, F., Levy, D., Lerner, A., Rondanini, G. F., Dupont, B., and New, M. I., 1982, Late-onset steroid 21-hydroxylase deficiency: A variant of classical congenital adrenal hyperplasia, J. Clin. Endocrinol. Metab. 51: 817–827.
Kominami, S., Ochi, H., Kobayashi, Y., and Takemori, S., 1980, Studies on the steroid hydroxylation system in adrenal cortex microsomes: Purification and characterization of cytochrome P450 specific for steroid 21 hydroxylation, J. Biol. Chem. 255: 3386–3394.
Kutten, F., Couillin, P., Girard, F., Billaud, L., Vincens, M., Boucekkine, C., Thalabard, J.-C., Maudelonde, T., Spritzer, P., Mowszowicz, I., Boué, A., and Mauvais-Jarvis, P., 1985, Late-onset adrenal hyperplasia in hirsutism, N. Engl. J. Med. 313: 222–231.
Kwok, S., Kellogg, D. E., McKinney, N., Spasic, D., Goda, L., Levenson, C., and Sninsky, J. J., 1990, Effect of primer-template mismatches on the polymerase chain reaction: Human immunodeficiency virus type 1 model studies, Nucleic Acids Res. 18: 999–1005.
Lambeth, J. D., and Pember, S. O., 1983, Cytochrome P-450scc-adrenodoxin complex: Reduction properties of the substrate-associated cytochrome and relation of the reduction states of heme and iron-sulfur centers to association of the proteins, J. Biol. Chem. 258: 5596–5602.
Lambeth, J. D., Seybert, D., and Kamin, H., 1979, Ionic effects on adrenal steroidogenic electron transport: The role of adrenodoxin as an electron shuttle, J. Biol. Chem. 254: 7255–7264.
Levine, L. S., and 22 co-authors, 1980, Cryptic 21-hydroxylase deficiency in families of patients with classical congenital adrenal hyperplasia, J. Clin. Endocrinol. Metab. 51: 1316.
Levine, L. S., Dupont, B., Lorenzen, F., Pang, S., Pollack, M. S., et al, 1981a, Genetic and hormonal characterization of the cryptic 21-hydroxylase deficiency, J. Clin. Endocrinol Metab. 53: 1193–1198.
Lévi-Strauss, M., Carroll, M. C., Steinmetz, M., and Meo, T., 1988, A previously undetected MHC gene with an unusual periodic structure, Science 240: 201–204.
Li, X., Warren, D. W., Gregorie, J., Pedersen, R. C., and Lee, A. S., 1989, 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. 3: 1944–1952.
Liebhaber, S. A., Goossens, M., and Kan, Y. W., 1981, Homology and concerted evolution of the a-1 and a-2 locus of human a-globin, Nature 290: 26–29.
Lin, D., Shi, Y., and Miller, W. L., 1990, Cloning and sequence of the human adrenodoxin reductase gene, Proc. Natl. Acad. Sci. USA 87: 8516–8520.
Lin, D., Harikrishna, J. A., Moore, C. C. D., Jones, K. L., and Miller, W. L., 1991cr, Missense mutation serine 106 proline causes 17d-hydroxylase deficiency, J. Biol. Chem. 266: 15992–15998.
Lin, D., Gitelman, S. E., Saenger, P., and Miller, W. L., 19916, Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia, J. Clin. Invest., in press.
Lorence, M. C., Murry, B. A., Trant, J. M., and Mason, J. I., 1990, Human 3b- hydroxysteroid dehydrogenase/A5A 4 isomerasefrom placenta: Expression in nonsteroi- dogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids, Endocrinology 126: 2493–2498.
Luu-The, V., Lachance, Y., Labrie, C., Leblanc, G., Thomas, J. L., Strickler, R. C., and Labrie, F., 1989, Full length cDNA structure and deduced amino acid sequence of human 3/3-hydroxy-5-ene steroid dehydrogenase, Mol. Endocrinol. 3: 1310–1312.
Mason, J. I., and Rainey, W. E., 1987, Steroidogenesis in the human fetal adrenal: A role for cholesterol synthesized de novo, J. Clin. Endocrinol. Metab. 64: 149–147.
Matsumoto, T., Kondoh, T., Kamel, T., Yoshimoto, M., Tsuji, Y., Suzumore, K., Izumi, R., Iwantani, N., and Nikawa, N., 1988, Prenatal DNA analysis in four embryos/fetuses at risk of 21-hydroxylase deficiency, Eur. J. Pediatr. 148: 228–232.
Matteson, K. J., Chung, B., Urdea, M. S., and Miller, W. L., 1986a, Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia, using bovine-sequence P450scc oligodeoxyribonucleotide probes, Endocrinology 118: 1296–1305.
Matteson, K. J., Picado-Leonard, J., Chung, B., Mohandas, T. K., and Miller, W. L., 19866, Assignment of the gene for adrenal P450cl7 (17a-hydroxylase/17,20 lyase) to human chromosome 10, J. Clin. Endocrinol. Metab. 63: 789–791.
Matteson, K. J., Phillips, J. A., Ill, Miller, W. L., Chung, B., Orlando, P. J., Frisch, H., Ferrandez, A., and Burr, I. M., 1987, P450XXI (steroid 21-hydroxylase) gene deletions are not found in family studies of congenital adrenal hyperplasia, Proc. Natl. Acad. Sci. USA 84: 5858–5862.
McLean, R. H., Donohue, P., Jospe, N., Bias, W. B., Van Dop, C., and Migeon, C. J., 1988, Restriction fragment analysis of duplication of the fourth component of complement (C4A), Genomics 2: 76–85.
McLean, R. H., Bias, W. B., Giles, C., Yu, C. Y., and Campbell, R. D., 1990, Characterization of 2 hybrid C4 allotypes (C4*12 and C4B*3) by electrophoretic, serological and restriction fragment length polymorphism analyses, Tissue Antigens 35: 75–81.
Mellon, S. H., and Miller, W. L., 1989, Extra-adrenal steroid 21-hydroxylation is not mediated by P450c21, J. Clin. Invest. 84: 1497–1502.
Migeon, C. J., 1990, Comments about the need for prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, J. Clin. Endocrinol. Metab. 70: 836–837.
Migeon, C. J., Rosenwask, Z., Lee, P. A., Urban, M. D., and Bias, W. B., 1980, The attenuated form of congenital adrenal hyperplasia as an allelic form of 21-hydroxylase deficiency, J. Clin. Endocrinol. Metab. 51: 647–649.
Miller, W. L., 1988(7, Molecular biology of steroid hormone synthesis, Endocr. Rev. 9: 295–318.
Miller, W. L., 19886, Gene conversions, deletions, and polymorphisms in congenital adrenal hyperplasia, Am. J. Hum. Genet. 42: 4–7.
Miller, W. L., and Eberhardt, N. L., 1983, Structure and evolution of the growth hormone gene family, Endocr. Rev. 4: 97–130.
Miller, W. L., and Levine, L. S., 1987, Molecular and clinical advances in congenital adrenal hyperplasia, J. Pediatr. 111: 1–17.
Miller, W. L., and Morel, Y., 1989, Molecular genetics of 21-hydroxylase deficiency, Annu. Rev. Genet. 23: 371–393.
Monier, S., VanLuc, P., Kreibich, G., Sabatini, D. D., and Adesnik, M., 1988, Signals for incorporation and orientation of cytochrome P450 in the endoplasmic reticulum membrane, J. Cell Biol. 107: 457–470.
Moore, C. C. D., and Miller, W. L., 1991, The role of transcriptional regulation in steroid hormone biosynthesis, J. Steroid Biochem., in press.
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-tetradecanolyphorbol-13-acetate and A23187 by independent c/s-elements, Mol. Cell. Biol. 10: 6013–6023.
Morel, Y., Picado-Leonard, J., Wu, D. A., Chang, C., Mohandas, T. K., Chung, B., and Miller, W. L., 1988, Assignment of the functional gene for adrenodoxin to chromosome llql.3-qterm and of two adrenodoxin pseudogenes to chromosome 20cen—13.1, Am. J. Hum. Genet. 43: 52–59.
Morel, Y., Andre, J., Uring-Lambert, B., Hauptman, G., Betuel, H., Tosi, M., Forest, M. G., David, M., Bertrand, J., and Miller, W. L., 1989a, Rearrangements and point mutations of P450c21 genes are distinguished by five restriction endonuclease haplotypes identified by a new probing strategy in 57 families with congenital adrenal hyperplasia, J. Clin. Invest. 83: 527–536.
Morel, Y., David, M., Forest, M. G., Betuel, H., Hauptman, G., Andre, J., Bertrand, J., and Miller, W. L., 19896, Gene conversions and rearrangements cause discordance between inheritance of forms of 21-hydroxylase deficiency and HLA types, J. Clin. Endocrinol. Metab. 68: 592–599.
Morel, Y., Bristow, J., Gitelman, S. E., and Miller, W. L., 1989c, Transcript encoded on the opposite strand of the human 21-hydroxylase/C4 locus, Proc. Natl. Acad. Sci. USA 86: 6582–6586.
Morel, Y., Murena, M., Forest, M. G., and David, M., 1990, The molecular genetic studies of 21-hydroxylase deficiency (CAH): An update and usefulness for prenatal diagnosis, Hormone Res. 33 (suppl. 2): 52.
Morel, Y., Murena, M., Forest, M. G., Nicolino, M., and David, M., 1991, Frequency of the 8 known deleterious point mutations of the CYP21B gene in more than 100 families with 21-hydroxylase deficiency (CAH): Implications for prenatal diagnosis, The Endocrine Society, 73rd Annual Meeting, Atlanta, Georgia, Abstract 1379.
Mornet, E., Boue, J., Raux-Demay, M., Couillin, P., Oury, J., Dumez, Y., Dausset, J., Cohen, D., and Boue, A., 1986a, First trimester prenatal diagnosis of 21-hydroxylase deficiency by linkage analysis of HLA-DNA probes and by 17-hydroxyprogesterone determination, Hum. Genet. 73:358–-364.
Mornet, E., Couillin, P., Kutten, F., Raux-Demay, M. C., White, P., Cohen, D., Boue, A., and Dausset, J., 19866, Associations between restriction fragment length polymorphisms detected with a probe for human 21-hydroxylase (21-OH) and two clinical forms of 21-OH deficiency, Hum. Genet. 74: 402–408.
Mornet, E., Dupont, J., Vitek, A., and White, P. C., 1989, Characterization of two genes encoding human steroid 11-beta-hydroxylase (P-450-1 lbeta), J. Biol. Chem. 264: 20961–20967.
Mornet, E., Crete, P., Kuttenn, F., Raux-Demay, M. C., Bou, J., White, P. C., and Boue, A., 1991, Distribution of deletions and seven point mutations on CYP21B genes in three clinical forms of steroid 21-hydroxylase deficiency, Am. J. Hum. Genet. 48: 79–88.
Morohashi, K., Sogawa, K., Omura, T., and Fujii-Kuriyama, Y., 1987, Gene structure of human cytochrome P-450(SCC), cholesterol desmolase, /. Biochem. 101: 879–887.
Mulaikal, R. M., Migeon, C. J., and Rock, J. A., 1987, Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, N. Engl. J. Med. 316: 178–182.
Nakajin, S., Shively, J. E., Yuan, P., and Hall, P. F., 1981, Microsomal cytochrome P450 from neonatal pig testis: Two enzymatic activities (17a-hydroxylase and C17,20-lyase) associated with one protein, Biochemistry 20: 4037–4042.
Nebert, D. W., and Gonzalez, F. J., 1987, P450 genes: Structure, evolution and regulation, Annu. Rev. Biochem. 56: 945–993.
Nebert, D. W., Adesnik, M., Coon, M. J., Estabrook, R. W., Gonzalez, F. J., Guengerich, F. P., Gunsalus, I. C., Johnson, E. F., Kemper, B., Levin, W., Phillips, I. R., Sato, R., and Waterman, M. R., 1987, The P450 gene superfamily: Recommended nomenclature, DNA 6: 1–11.
Nebert, D. W., Adesnik, M., Coon, M. J., Estabrook, R. W., Gonzalez, F. J., Guengerich, F. P., Gunsalus, I. C., Johnson, E. F., Kemper, B., Levin, W., Phillips, I. R., Sato, R., and Waterman, M. R., 1989, The P450 superfamily: Updated listing of all genes and recommended nomenclature for the chromosomal loci, DNA 8: 1–13.
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 450 superfamily: Update on new sequences, gene mapping, and recommended nomenclature, DNA Cell Biol. 10: 1–14.
New, M. I., DuPont, B., Pang, S., Pollack, M. S., and Levine, L. S., 1981, An update of congenital adrenal hyperplasia, Rec. Prog. Hormone Res. 37: 105–181.
New, M. I., Dupont, B., Grumbach, K., and Levine, L. S., 1982, Congenital adrenal hyperplasia and related conditions, in: The Metabolic Basis of Inherited Disease, 5th ed. (J. B. S. Stanbury, J. B., Wyngarden, D. S. Fredrickson, J. F., Goldstein, and M. S. Brown, eds., McGraw-Hill, New York, pp. 973–1000.
New, M., White, P., Pang, S., Dupont, B., and Speiser, P., 1989, The adrenal hyperplasias, in: The Metabolic Basis of Inherited Disease ( C. Scriver, A. Beaudet, W. Sly, and D. Valle, eds.), McGraw-Hill, New York, pp. 1881–1917.
New, M. I., Mercado, A. B., Wood, E., Buegeleisen, M., Karaviti, L. P., and Speiser, P. W., 1990, Prenatal diagnosis of 21-hydroxylase deficiency when the parent is the patient, The Endocrine Society, 72nd Annual Meeting, Atlanta, Georgia, Abstract 1458.
Nicolas, A., Treco, D., Schultes, N. P., and Szostak, J. W., 1989, An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae, Nature 338: 35–39.
Noland, B. J., Arebalo, R. E., Hansbury, E., and Scallen, T. J., 1980, Purification and properties of sterol carrier protein, J. Biol. Chem. 255: 4282–4289.
Olerup, O., Luthman, H., Ritzen, E. M., and Haglund-Stengler, B., 1990, Taq I HLA-B and HLA-Drb RFLP analysis can predict disease in siblings of affected children with 21-hydroxylase deficiency, Hum. Genet. 85: 467–472.
Onoda, M., and Hall, P. F., 1982, Cytochrome b5 stimulates purified testicular microsomal cytochrome P-450 (C21 side-chain cleavage), Biochem. Biophys. Res. Commun. 108: 454–460.
Oprian, D. D., and Coon, M. J., 1982, Oxidation-reduction states of FMN and FAD in NADPH-cytochrome P-450 reductase during reduction by NADPH, J. Biol. Chem. 257: 8935–8944.
Owerbach, D., Crawford, Y. M., and Draznin, M. B., 1990, Direct analysis of CYP21B genes in 21-hydroxylase deficiency using polymerase chain reaction amplification, Mol. Endocrinol. 4: 125–131.
Palsdottir, A., Arnason, A., Fossdal, R., and Jensson, O., 1987, Gene organization of haplotypes expressing two different C4A allotypes, Hum. Genet. 76: 220–224.
Pang, S. Y., and Clark, A., 1990, Newborn screening, prenatal diagnosis, and prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, Trends Endocrinol. Metab. 1: 300–307.
Pang, S., Levine, L. S., Cederquist, K. K., Fuentes, M., Riccari, V. M., Holcombe, J. H., Nitowski, H. M., Sachs, G., Anderson, C. E., Duchon, M. A., Owens, R., Merkatz, I., and New, M. I., 1980, Amniotic fluid concentrations of A5 and A4 steroids in fetuses with congenital adrenal hyperplasia due to 21-hydroxylase deficiency and in anencephalic fetuses, J. Clin. Endocrinol. Metab. 51: 223–229.
Pang, S., Pollack, M. S., Loo, M., Green, O., Nussbaum, R., Clayton, G., Dupont, B., and New, M. I., 1985, Pitfalls of prenatal diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia, J. Clin. Endocrinol. Metab. 61: 89–97.
Pang, S., Wallace, M. A., H of man, L., Thuline, H. C., Dorche, C., Lyon, I. C. T., Dobbind, R. H., Kling, S., Fujieda, K., and Suwa, S., 1988, Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency, Pediatrics 81: 866–874.
Pang, S., Pollack, M. S., Marshall, R. N., and Immken, L. D., 1990, Prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, N. Engl. J. Med. 322: 111–115.
Parker, K. L., Chaplin, D. D., Wong, M., Seidman, J. G., Smith, J. A., and Schimmer, B. P., 1985, Expression of murine 21-hydroxylase in mouse adrenal glands and in transfected Y1 adrenocortical tumor cells, Proc. Natl. Acad. Sci. USA 82: 7860–7864.
Partanen, J., Kere, J., Wessberg, S., and Koskimies, S., 1989a, Determination of deletion sizes in human C4 and CYP21 genes using pulsed field gel electrophoresis, Genomics 5: 345–349.
Partanen, J., Koskimies, S., Sipila, I., and Lipsanen, V., 1989b, Major histocompatibility- complex gene markers and restriction-fragment analysis of steroid 21-hydroxylase (CYP21) and complement C4 genes in classical congenital adrenal hyperplasia patients in a single population, Am. J. Hum. Genet. 44: 660–670.
Pedersen, R. C., and Brownie, A. C., 1983, Cholesterol side-chain cleavage in the rat adrenal cortex: Isolation of a cycloheximide-sensitive activator peptide, Proc. Natl. Acad. Sci. USA 80: 1882–1886.
Pedersen, R. C., and Brownie, A. C., 1987, Steroidogenesis-activator polypeptide isolated from a rat Leydig cell tumor, Science 236: 188–190.
Phillips, J. A., Ill, Burr, I. M., Orlando, P., Matteson, K. J., Chung, B., and Miller, W. L., 1985, DNA analysis of human steroid 21-hydroxylase genes in congenital steroid 21-hydroxylase and controls using a bovine genomic clone, Am. J. Hum. Genet. 37:A171, Abstract 505.
Picado-Leonard, J., and Miller, W. L., 1987, Cloning and sequence of the human gene for P450cl7 (steroid 17a-hydroxylase/17,20 lyase): Similarity to the gene for P450c21, DNA 6: 437–446.
Picado-Leonard, J., and Miller, W. L., 1988, Homologous sequences in steroidogenic enzymes, steroid receptors and a steroid binding protein suggest a consensus steroid- binding sequence, Mol. Endocrinol. 2: 1145–1150.
Picado-Leonard, J., Voutilainen, R., Kao, L., Chung, B., Strauss, J. F., Ill, and Miller, W. L., 1988, Human adrenodoxin: Cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells, J. Biol. Chem. 263:3240–3244; corrected, p. 11016.
Pollack, M. S., Levine, L. S., Pang, S., and Owens, R. P., 1979, Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) by HLA typing, Lancet 1: 1107–1108.
Pollack, M. S., Levine, L. S., and O’Neill, G. L., 1981, HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency, Am. J. Hum. Genet. 33: 540–550.
Privalle, C. T., Crivello, J. F., and Jefcoate, C. R., 1983, Regulation of intramitochondrial cholesterol transfer to side-chain cleavage cytochrome P-450 in rat adrenal gland, Proc. Natl. Acad. Sci. USA 80: 702–706.
Pucholt, V., Fitzsimmons, J. S., Reynolds, M. A., and Gelsthorpe, K., 1979, Location of the gene for 21-hydroxylase deficiency, Pediatr. Res. 13: 1186.
Radding, C. M., 1978, Genetic recombination: Strand transfer and mismatch repair, Annu. Rev. Biochem. 47: 847–880.
Rodrigues, N. R., Dunham, I., Yu, C. Y., Carroll, M. C., Porter, R. R., and Campbell, R. D., 1987, Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene from an individual with congenital adrenal hyperplasia, EMBO J. 6: 1653–1661.
Rosenbloom, N. R., and Smith, D. W., 1966, Varying expression for salt-losing in related patients with congenital adrenal hyperplasia, Pediatrics 38: 215–219.
Rosenfeld, R. L., and Miller, W. L., 1983, Hirsutism and Virilism (V. B. Mahesh and R. B. Greenblatt, eds. ), Wright-PSG. pp. 87–119.
Rumsby, G., and Honour, J. W., 1990, In vitro gene amplification for prenatal diagnosis of congenital adrenal hyperplasia, J. Med. Genet. 27: 676–678.
Rumsby, G., Carroll, M. C., Porter, R. R., Grant, D. B., and Hjelm, M., 1986, Deletion of steroid 21-hydroxylase and complement C4 genes in congenital adrenal hyperplasia, J. Med. Genet. 23: 204–209.
Saenger, P., 1984, Abnormal sex differentiation, J. Pediatr. 104: 1–17.
Sakaki, T., Shibata, M., Yabusaki, Y., Murakami, H., and Ohkawa, H., 1989, Expression of bovine cytochrome P450cl7 cDNA in Saccharomyces cerevisiae, DNA 8: 409–418.
Sargent, C. A., Dunham, I., and Campbell, R. C., 1989, Identification of multiple HTF-island associated genes in the major histocompatibility complex class III region, EMBO J. 8: 2305–2312.
Scallen, T. J., Noland, B. J., Gavey, K. L., Bass, N. M., Ockner, R. K., Chanderbhan, R., and Vahouny, G. V., 1985, Sterol carrier protein 2 and fatty acid-binding protein: Separate and distinct physiological functions, J. Biol. Chem. 260: 4733–4739.
Schneider, P. M., and Rittner, C., 1988, Bgl II restriction fragment length polymorphism of human complement C4 gene coincides with Bf*F allele of factor B, Immunogenetics 27: 225–228.
Schneider, P. M., Carroll, M. C., Alper, C. A., Rittner, C., Whitehead, A. S., Yunis, E. J., and Colten, H. R., 1986, Polymorphism of the human complement C4 and steroid 21-hydroxylase genes, J. Clin. Invest. 78: 650–657.
Sherman, S. L., Aston, C. E., Morton, N. E., Speiser, P. W., and New, M. I., 1988, A segregation and linkage study of classical and nonclassical 21-hydroxylase deficiency, Am. J. Hum. Genet. 42: 830–838.
Shima, S., Mitsunaga, M., and Nakao, T., 1972, Effect of ACTH on cholesterol dynamics in rat adrenal tissue, Endocrinology 90: 808–814.
Simpson, E. R., 1979, Cholesterol side-chain cleavage, cytochrome P450, and the control of steroidogenesis, Mol. Cell. Endocrinol. 13: 213–227.
Sinnott, P. J., Dyer, P. A., Price, D. A., Harris, R., and Strachan, T., 1989, 21-Hydroxylase deficiency families with HLA identical affected and unaffected sibs, J. Med. Genet. 26: 10–17.
Sinnott, P., Collier, S., Costigan, C., Dyer, P. A., Harris, R., and Strachan, T., 1990, Genesis by meiotic unequal crossover of a de novo deletion that contributes to steroid 21-hydroxylase deficiency, Proc. Natl. Acad. Sci. USA 87: 2107–2111.
Sklar, C. A., Kaplan, S. L., and Grumbach, M. M., 1980, Evidence for dissociation between adrenarche and gonadarche: Studies in patients with idiopathic precocious puberty, gonadal dysgenesis, isolated gonadotropin deficiency, and constitutionally delayed growth and adolescence, J. Clin. Endocrinol. Metab. 51: 548–556.
Skow, L. E., Womack, J. E., Petresh, J. M., and Miller, W. L., 1988, Synteny mapping of the genes for steroid 21-hydroxylase, alpha-A-crystallin, and class I bovine leukocyte antigen (BoLA) in cattle, DNA 7: 143–149.
Slightom, J. L., Blechl, A. E., and Smithies, O., 1980, Human fetal;gg- and a-globin genes: Complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes, Cell 21: 627–638.
Solish, S. B., Picado-Leonard, J., Morel, Y., Mohandas, T. K., Honakoglu, I., and Miller, W. L., 1988, Human adrenodoxin reductase: Two mRNAs encoded by a single gene on chromosome 17cenq25 are expressed in steroidogenic tissues, Proc. Natl. Acad. Sci. USA 85: 7104–7108.
Solish, S. B., Goldsmith, M. A., Voutilainen, R., and Miller, W. L., 1989, Molecular characterization of a Leydig cell tumor presenting as congenital adrenal hyperplasia, J. Clin. Endocrinol. Metab. 69: 1148–1152.
Sparkes, R. S., Klisak, K. I., and Miller, W. L., 1991, Regional mapping of genes encoding steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to llq22, adrenodoxin reductase to 17q24-q25, and P450cl7 to 10q24-q25, DNA Cell Biol. 10: 359–365.
Speiser, P. W., and White, P. C., 1989, Structure of the human RD gene: A highly conserved gene in the class III region of the major histocompatibility, DNA 8: 745–751.
Speiser, P. W., Dupont, B., Rubinstein, P., Piazza, A., Kastelan, A., and New, M. I., 1985, High frequency of nonclassical steroid 21-hydroxylase deficiency, Am. J. Hum. Genet. 37: 650–667.
Speiser, P. W., New, M. I., and White, P., 1988, Molecular genetic analysis of nonclassical steroid 21-hydroxylase deficiency associated with HLA-B14DR1, N. Engl. J. Med. 319: 19–23.
Speiser, P. W., Laforgia, N., Kato, K., Pareira, J., Khan, R., Yang, S. Y., Whorwood, C., White, P. C., Elias, S., Schriock, E., Simpson, J. L., Taslimi, M., Najjar, J., May, S., Mills, G., Crawford, C., and New, M. I., 1990, First trimester prenatal treatment and molecular genetic diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency), J. Clin. Endocrinol. Metab. 70: 838–848.
Speiser, P. W., Agdere, L., Ueshiba, H., White, P. C., and New, M. I., 1991, Aldosterone synthesis in patients with salt-wasting congenital adrenal hyperplasia (21-hydroxylase deficiency) and complete absence of adrenal 21-hydroxylase (P450c21), N. Engl. J. Med. 324: 145–149.
Spies, T., Blanck, G., Bresnarhan, M., Sands, J., and Strominger, J. L., 1989, A new cluster of genes within the human major histocompatibility complex, Science 243: 214–217.
Stoeckert, C. J., Jr., Collins, F. S., and Weissman, S. M., 1984, Human fetal globin DNA synthesis in adrenal fasciculata cells, Endocr. Res. 12: 315–350.
Stoner, E., DiMartina, J., Kuhnle, U., Levine, L. S., Oberfield, S. E., and New, M. I., 1986, Is salt-wasting in congenital adrenal hyperplasia genetic?, Clin. Endocrinol. 24: 9–20.
Strachan, T., 1990, Molecular pathology of congenital adrenal hyperplasia, Clin. Endocrinol. 32: 373–393.
Strachan, T., Sinnott, P. J., Smeaton, I., Dyer, P. A., and Harris, R., 1987, Prenatal diagnosis of congenital adrenal hyperplasia, Lancet 11: 1272–1273.
Strauss, J. F., Ill, and Miller, W. L., 1991, Molecular basis of ovarian steroid synthesis, in: Ovarian Endocrinology ( S. G. Hillier, ed.), Blackwell Scientific, Oxford, pp. 25–72.
Szostak, J. W., Orr-Weaver, T. L., and Rothstein, R. J., 1983, The double-stranded-break repair model for recombination, Cell 33: 25–35.
Tamburini, P. P., and Gibson, G. G., 1983, Thermodynamic studies of the protein-protein interactions between cytochrome P-450 and cytochrome b5, J. Biol. Chem. 258: 13444–13452.
Thomas, J. L., Myers, R. P., and Strickler, R. C., 1989, Human placental 3/3-hydroxy-5-ene steroid dehydrogenase and steroid-5-4-ene isomerase: Purification from mitochondria and kinetic profiles, biophysical characterization of the purified mitochondrial and microsomal enzymes, J. Steroid Biochem. 33: 209.
Ting, J., and Lee, A. S., 1988, Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: Structure, conservation, and regulation, DNA 7: 275–286.
Tokunaga, K., Saueracker, G., Kay, P. H., Christiansen, F. T., Anand, R., and Dawkins, R. L., 1988, Extensive deletions and insertions in different MHC supratypes detected by pulsed field gel electrophoresis, J. Exp. Med. 168:933–940.
Townsend, S., Dallman, M. F., and Miller, W. L., 1990, Rat insulin-like growth factor -I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth, J. Biol. Chem. 265: 22117–22122.
Trzeciak, W. H., Mason, J. I., and Boyd, G. S., 1979, Effect of hypophysectomy and corticotropin replacement on sterol ester hydrolase activity from rat adrenal gland, FEBS Lett. 102: 1–17.
Tukey, R. H., Okino, S., Barnes, H., Griffin, K. J., and Johnson, E. F., 1985, Multiple gene-like sequences related to the rabbit hepatic progesterone 21-hydroxylasecytochrome P-450 1, J. Biol. Chem. 260: 13347–13354.
Urabe, K., Kimura, A., Harada, F., Iwanaga, T., and Sasazuki, T., 1990, Gene conversion in steroid 21-hydroxylase genes, Am. J. Hum. Genet. 46: 1178–1186.
Voutilainen, R., and Miller, W. L., 1986, Developmental expression of genes for the steroidogenic enzymes P450scc (20,22 desmolase), P450cl7 (17a-hydroxylase/17,20 lyase) and P450c21 (21-hydroxylase) in the human fetus, J. Clin. Endocrinol. Metab. 63: 1145–1150.
Voutilainen, R., and Miller, W. L., 1987, Coordinate tropic hormone regulation of mRNAs for insulin-like growth factor II and the cholesterol side-chain cleavage enzyme, P450scc, in human steroidogenic tissues, Proc. Natl. Acad. Sci. USA 84: 1590–1594.
Voutilainen, R., Tapanainen, J., Chung, B., Matteson, K. J., and Miller, W. L., 1986, Hormonal regulation of P450scc (20,22 desmolase) and P450cl7 (17a-hydroxylase/17,20 lyase) in cultured human granulosa cells, J. Clin. Endocrinol. Metab. 63: 202–207.
Werkmeister, J. W., New, M. I., Dupont, B., and White, P. C., 1986, Frequent deletions and duplication of the steroid 21-hydroxylase genes, Am. J. Hum. Genet. 39: 461–469.
White, P. C., New, M. I., and Dupont, B., 1984, HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P450 specific for steroid 21- hydroxylation, Proc. Natl. Acad. Sci. USA 81: 7505 - 7509.
White, P. C., Grossberger, D., Onufer, B. J., Chaplin, D. D., New, M. I., Dupont, B., and Strominger, J. L., 1985, Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of the complement in man, Proc. Natl. Acad. Sci. USA 82: 1089–1093.
White, P. C., New, M. I., and Dupont, B., 1986, Structure of the human 21-hydroxylase genes, Proc. Natl. Acad. Sci. USA 83: 5111–5115.
White, P. C., Vitek, B., Dupont, B., and New, M. I., 1988, Characterization of frequent deletions causing steroid 21-hydroxylase deficiency, Proc. Natl. Acad. Sci. USA 85: 4436–4440.
Wu, D. A., and Chung, B., 1991, Mutations of P450c21 at Cys428, Val281, or Ser268 result in complete, partial, or no loss of enzymatic activity, J. Clin. Invest. 88: 519–523.
Wu, D. A., Hu, M. C., and Chung, B., 1991, Expression and functional study of wild-type and mutant human cytochrome P450c21 in Saccharomyces cerevisiae, DNA Cell Biol. 10: 201–209.
Yamano, S., Aoyama, T., McBride, O. W., Hardwick, J. P., Gelboin, H. V., and Gonzalez, F. J., 1989, Human NADPH-P450 oxidoreductase: Complementary DNA cloning, sequence, vaccinia virus-mediated expression, and localization of the CYPOR gene to chromosome 7, Mol. Pharmacol. 35: 83–88.
Yanagibashi, K., and Hall, P. F., 1986, Role of electron transport in the regulation of the lyase activity of C21 side-chain cleavage P-450 from porcine adrenal and testicular microsomes, Biol. Chem. 261: 8429–8433.
Yanagibashi, K., Haniu, M., Shively, J. E., Shen, W. H., and Hall, P., 1986, The synthesis of aldosterone by the adrenal cortex: Two zones (fasciculata and glomerulosa) possess one enzyme for 11-, 18-hydroxylation, and aldehyde synthesis, J. Biol. Chem. 261: 3556–3562.
Yanagibashi, K., Ohno, Y., Kawamura, M., and Hall, P. F., 1988, The regulation of intracellular transport of cholesterol in bovine adrenal cells: Purification of a novel protein, Endocrinology 123: 2075–2082.
Yu, Y. C., and Campbell, R. D., 1987, Definitive RFLPs to distinguish between the human complement C4A/C4B isotypes and the major radgers/chido determinants: Application to the study of C4 null alleles, Immunogenetics 25: 383–390.
Yu, Y. C., Belt, K. T., Giles, C. M., Campbell, R. D., and Porter, R. R., 1986, Structural basis of the polymorphism of the human complement components C4A and C4B: Gene size, reactivity and antigenicity, EMBO J. 5: 2873–2881.
Zachmann, M., Vollmin, J. A., Hamilton, W., and Prader, A., 1972, Steroid 17,20 desmolase deficiency: A new cause of male pseudohermaphroditism, Clin. Endocrinol. 1: 369–385.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Morel, Y., Miller, W.L. (1991). Clinical and Molecular Genetics of Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. In: Harris, H., Hirschhorn, K. (eds) Advances in Human Genetics. Advances in Human Genetics, vol 20. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5958-6_1
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5958-6_1
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5960-9
Online ISBN: 978-1-4684-5958-6
eBook Packages: Springer Book Archive