WALTER MILLER

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Cortisol response to operative stress with anesthesia in healthy children
    Lisa K Taylor
    Department of Pediatrics, HSE 1401, 513 Parnassus Avenue, University of California, San Francisco, San Francisco, California 94143 0978
    J Clin Endocrinol Metab 98:3687-93. 2013
  2. doi request reprint Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA Electronic address
    Am J Obstet Gynecol 208:354-9. 2013
  3. doi request reprint A brief history of adrenal research: steroidogenesis - the soul of the adrenal
    Walter L Miller
    University of California, San Francisco, San Francisco, USA
    Mol Cell Endocrinol 371:5-14. 2013
  4. doi request reprint P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations
    Walter L Miller
    University of California, San Francisco, San Francisco, CA 94143 0978, USA
    Sci Signal 5:pt11. 2012
  5. pmc Varied clinical presentations of seven patients with mutations in CYP11A1 encoding the cholesterol side-chain cleavage enzyme, P450scc
    Meng Kian Tee
    Department of Pediatrics, University of California, San Francisco, San Francisco, California, 94143, USA
    J Clin Endocrinol Metab 98:713-20. 2013
  6. pmc Early steps in steroidogenesis: intracellular cholesterol trafficking
    Walter L Miller
    Department of Pediatrics, School of Medicine, University of California, San Francisco, CA 94143, USA
    J Lipid Res 52:2111-35. 2011
  7. pmc The syndrome of 17,20 lyase deficiency
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 97:59-67. 2012
  8. ncbi request reprint StAR search--what we know about how the steroidogenic acute regulatory protein mediates mitochondrial cholesterol import
    Walter L Miller
    Department of Pediatrics, Box 0978, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Mol Endocrinol 21:589-601. 2007
  9. doi request reprint Role of mitochondria in steroidogenesis
    Walter L Miller
    Department of Pediatrics, University of California San Francisco, CA 94143, USA
    Endocr Dev 20:1-19. 2011
  10. doi request reprint Consequences of POR mutations and polymorphisms
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143 0978, USA
    Mol Cell Endocrinol 336:174-9. 2011

Research Grants

  1. Molecular Biology of Steroidogenic Proteins
    WALTER MILLER; Fiscal Year: 2005
  2. ANDROGEN PRODUCTION IN ADRENARCHE AND PCOS
    WALTER MILLER; Fiscal Year: 2006
  3. Pharmacogenomics of Human P450 Oxidoreductase
    WALTER MILLER; Fiscal Year: 2007
  4. TRAINING GRANT IN PEDIATRIC ENDOCRINOLOGY
    WALTER MILLER; Fiscal Year: 2007
  5. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 2007
  6. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 2009
  7. Pharmacogenomics of Human P450 Oxidoreductase
    WALTER MILLER; Fiscal Year: 2009
  8. Pharmacogenomics of Human P450 Oxidoreductase
    WALTER MILLER; Fiscal Year: 2009
  9. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    Walter L Miller; Fiscal Year: 2010
  10. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 1990

Collaborators

Detail Information

Publications81

  1. pmc Cortisol response to operative stress with anesthesia in healthy children
    Lisa K Taylor
    Department of Pediatrics, HSE 1401, 513 Parnassus Avenue, University of California, San Francisco, San Francisco, California 94143 0978
    J Clin Endocrinol Metab 98:3687-93. 2013
    ..Peak cortisol levels were seen 1 hour postoperatively. These data suggest that current guidelines for stress dosing in adrenally insufficient patients substantially exceed physiological requirements during minimally invasive procedures. ..
  2. doi request reprint Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA Electronic address
    Am J Obstet Gynecol 208:354-9. 2013
    ....
  3. doi request reprint A brief history of adrenal research: steroidogenesis - the soul of the adrenal
    Walter L Miller
    University of California, San Francisco, San Francisco, USA
    Mol Cell Endocrinol 371:5-14. 2013
    ....
  4. doi request reprint P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations
    Walter L Miller
    University of California, San Francisco, San Francisco, CA 94143 0978, USA
    Sci Signal 5:pt11. 2012
    ..A promoter polymorphism reduces transcription to 60% in liver cells and to 35% in adrenal cells. POR deficiency is a newly described disorder of steroidogenesis, and POR variants may account for some genetic variation in drug metabolism...
  5. pmc Varied clinical presentations of seven patients with mutations in CYP11A1 encoding the cholesterol side-chain cleavage enzyme, P450scc
    Meng Kian Tee
    Department of Pediatrics, University of California, San Francisco, San Francisco, California, 94143, USA
    J Clin Endocrinol Metab 98:713-20. 2013
    ..P450scc deficiency can disrupt adrenal and gonadal steroidogenesis, resembling congenital lipoid adrenal hyperplasia clinically and hormonally; only 12 such patients have been reported previously...
  6. pmc Early steps in steroidogenesis: intracellular cholesterol trafficking
    Walter L Miller
    Department of Pediatrics, School of Medicine, University of California, San Francisco, CA 94143, USA
    J Lipid Res 52:2111-35. 2011
    ..Rare P450scc mutations cause a similar syndrome. This review addresses these early steps in steroid biosynthesis...
  7. pmc The syndrome of 17,20 lyase deficiency
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 97:59-67. 2012
    ..Beginning in 1972, several patients have been reported as having "17,20 lyase deficiency," but there have been inconsistent genetic findings...
  8. ncbi request reprint StAR search--what we know about how the steroidogenic acute regulatory protein mediates mitochondrial cholesterol import
    Walter L Miller
    Department of Pediatrics, Box 0978, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Mol Endocrinol 21:589-601. 2007
    ..The action of StAR probably requires interaction with the peripheral benzodiazepine receptor...
  9. doi request reprint Role of mitochondria in steroidogenesis
    Walter L Miller
    Department of Pediatrics, University of California San Francisco, CA 94143, USA
    Endocr Dev 20:1-19. 2011
    ..Rare mutations in P450scc result in both classic and non-classic hormonal syndromes that are indistinguishable from lipoid CAH, but have small adrenals...
  10. doi request reprint Consequences of POR mutations and polymorphisms
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143 0978, USA
    Mol Cell Endocrinol 336:174-9. 2011
    ..The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism...
  11. pmc The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders
    Walter L Miller
    Distinguished Professor of Pediatrics, University of California San Francisco, San Francisco, California 94143 0978, USA
    Endocr Rev 32:81-151. 2011
    ..Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis...
  12. doi request reprint Genetic variation in human P450 oxidoreductase
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, United States
    Mol Cell Endocrinol 300:180-4. 2009
    ..A503V reduces both activities of P450c17 in half, but had no effect on CYP1A2 or 2C19. POR variants are a previously unappreciated source of genetic variation in patterns of steroid synthesis and drug metabolism...
  13. ncbi request reprint Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter
    Walter L Miller
    Department of Pediatrics, Box 0978, University of California, San Francisco, CA 94122 0978, USA
    Biochim Biophys Acta 1771:663-76. 2007
    ..StAR appears to act in concert with the peripheral benzodiazepine receptor, but the precise itinerary of a cholesterol molecule entering the mitochondrion remains unclear...
  14. doi request reprint Androgen synthesis in adrenarche
    Walter L Miller
    Department of Pediatrics, University of California, Room 672 S, San Francisco, CA 94143 0978, USA
    Rev Endocr Metab Disord 10:3-17. 2009
    ....
  15. ncbi request reprint A pH-dependent molten globule transition is required for activity of the steroidogenic acute regulatory protein, StAR
    Bo Y Baker
    Department of Pediatrics and Metabolic Research Unit, University of California, San Francisco, California 94143, USA
    J Biol Chem 280:41753-60. 2005
    ..These data strongly support the model that StAR activity requires a pH-dependent molten globule transition on the OMM...
  16. pmc Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis
    Ningwu Huang
    Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143 0978, USA
    Am J Hum Genet 76:729-49. 2005
    ....
  17. ncbi request reprint P450 oxidoreductase deficiency: a new disorder of steroidogenesis affecting all microsomal P450 enzymes
    Amit V Pandey
    Department of Pediatrics, University of California San Francisco, San Francisco, California 94143 0978, USA
    Endocr Res 30:881-8. 2004
    ..POR deficiency is a new disorder of adrenal and gonadal steroidogenesis that affects all microsomal cytochrome P450 enzymes, hence may have important implications for genetic differences in drug metabolism...
  18. ncbi request reprint Rapid regulation of steroidogenesis by mitochondrial protein import
    Himangshu S Bose
    Department of Pediatrics, University of California, San Francisco, California 94143 0978, USA
    Nature 417:87-91. 2002
    ..This system enables steroidogenic cells to initiate and terminate massive levels of steroidogenesis within a few minutes, permitting the rapid regulation of serum steroid hormone concentrations...
  19. ncbi request reprint Regulation of cytochrome b5 gene transcription by Sp3, GATA-6, and steroidogenic factor 1 in human adrenal NCI-H295A cells
    Ningwu Huang
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Mol Endocrinol 19:2020-34. 2005
    ..Transcription of cytochrome b5 shares many features with the regulation of P450c17, whose activity it enhances...
  20. ncbi request reprint LBP proteins modulate SF1-independent expression of P450scc in human placental JEG-3 cells
    Ningwu Huang
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Mol Endocrinol 19:409-20. 2005
    ..LBP-1b is an important SF1-independent transcriptional activator stimulating P450scc expression in human placental JEG-3 cells, whereas LBP-9 modulates the action of LBP-1b, exerting both positive and negative effects...
  21. ncbi request reprint Mechanism of StAR's regulation of mitochondrial cholesterol import
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, CA 94143, United States
    Mol Cell Endocrinol 265:46-50. 2007
    ..Whereas many models have suggested that StAR delivers cholesterol to PBR, we suggest that StAR removes cholesterol from the cholesterol-binding domain of PBR and delivers it to the inner mitochondrial membrane...
  22. ncbi request reprint The steroidogenic acute regulatory protein, StAR, works only at the outer mitochondrial membrane
    Himangshu S Bose
    Department of Pediatrics, University of California, San Francisco, CA 94143 0978, USA
    Endocr Res 28:295-308. 2002
    ....
  23. doi request reprint Steroidogenic enzymes
    Walter L Miller
    Division of Endocrinology, Department of Pediatrics, University of California, San Francisco, CA 94142 0978, USA
    Endocr Dev 13:1-18. 2008
    ....
  24. ncbi request reprint Disorders of androgen synthesis--from cholesterol to dehydroepiandrosterone
    Walter L Miller
    Department of Pediatrics, University of California, San Francisco, California 94142 0978, USA
    Med Princ Pract 14:58-68. 2005
    ..Mutations of POR are a new, recently described disorder manifesting as the Antley-Bixler skeletal dysplasia syndrome, and a form of polycystic ovary syndrome...
  25. ncbi request reprint P450 oxidoreductase deficiency: a new disorder of steroidogenesis
    Walter L Miller
    Department of Pediatrics, Bldg MR IV, Room 209, University of California, San Francisco, San Francisco 94143 0978, USA
    Ann N Y Acad Sci 1061:100-8. 2005
    ..POR deficiency is a new disease, distinct from the craniosynostosis syndromes caused by FGFR mutations...
  26. ncbi request reprint P450 oxidoreductase deficiency: a new disorder of steroidogenesis with multiple clinical manifestations
    Walter L Miller
    Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143 0978, USA
    Trends Endocrinol Metab 15:311-5. 2004
    ..POR transfers electrons to all microsomal P450 enzymes: its deficiency affects steroidogenesis, drug metabolism and other processes...
  27. ncbi request reprint The mechanism of 1,25-dihydroxyvitamin D(3) autoregulation in keratinocytes
    Zhongjian Xie
    Endocrine Unit, Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA
    J Biol Chem 277:36987-90. 2002
    ..We believe this to be a unique mechanism for autoregulation of steroid hormone synthesis...
  28. ncbi request reprint Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17
    Amit V Pandey
    Department of Pediatrics, University of California, San Francisco, California 94143 0978, USA
    J Biol Chem 278:2837-44. 2003
    ..The identification of PP2A and SET as post-translational regulators of androgen biosynthesis suggests potential additional mechanisms contributing to adrenarche and hyperandrogenic disorders such as polycystic ovary syndrome...
  29. ncbi request reprint Androgen biosynthesis from cholesterol to DHEA
    Walter L Miller
    Department of Pediatrics, University of California, Bldg MR IV, Room 209, San Francisco 94142 0978, CA, USA
    Mol Cell Endocrinol 198:7-14. 2002
    ..Study of these and related factors may yield important information about the pathophysiology of adrenarche and the polycystic ovary syndrome (PCOS)...
  30. ncbi request reprint The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway
    Christa E Flück
    Department of Pediatrics and Metabolic Research Unit, University of California, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 88:3762-6. 2003
    ..We conclude that the majority of testosterone biosynthesis in the human testis proceeds through the conversion of pregnenolone to dehydroepiandrosterone via the delta(5) pathway...
  31. ncbi request reprint Vitamin D biosynthesis and vitamin D 1 alpha-hydroxylase deficiency
    Walter L Miller
    Department of Pediatrics, University of California San Francisco, San Francisco, Calif, USA
    Endocr Dev 6:156-74. 2003
  32. pmc Naturally-occurring mutation in the calcium-sensing receptor reveals the significance of extracellular domain loop III region for class C G-protein-coupled receptor function
    Qing Dong
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143 0434, USA
    J Clin Endocrinol Metab 95:E245-52. 2010
    ..Most mutations are clustered in the N-terminal and Cys-rich regions of the extracellular domain (ECD) and seven-transmembrane domain. Disease-causing mutations are uncommon in the C terminus of ECD...
  33. ncbi request reprint Regulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17
    Amit V Pandey
    Department of Pediatrics and the Metabolic Research Unit, University of California San Francisco, San Francisco, California 94143 0978, USA
    J Biol Chem 280:13265-71. 2005
    ..Cytochrome b5 and phosphorylation enhance 17,20 lyase activity independently of each other, probably by increasing the interaction between P450c17 and NADPH-cytochrome P450 oxidoreductase...
  34. ncbi request reprint Vitamin D 1alpha-hydroxylase gene mutations in patients with 1alpha-hydroxylase deficiency
    Chan Jong Kim
    Department of Pediatrics, University of California, San Francisco, 533 Parnassus Avenue, Box 0748, Room U 585, San Francisco, California 94143 0748, USA
    J Clin Endocrinol Metab 92:3177-82. 2007
    ..Each had clinical and radiographic features of rickets, hypocalcemia, and low serum concentrations of 1,25-dihydroxyvitamin D(3)...
  35. pmc Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients
    Taninee Sahakitrungruang
    Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA
    J Clin Endocrinol Metab 94:4992-5000. 2009
    ..P450 oxidoreductase (POR) deficiency causes disordered steroidogenesis; severe mutations cause genital ambiguity in both sexes plus the Antley-Bixler skeletal malformation syndrome, whereas mild mutations can cause adult infertility...
  36. ncbi request reprint Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency
    Rachel R Scott
    Pediatric Endocrinology, 672 S, University of California San Francisco, San Francisco, CA 94143 0434, USA
    J Clin Endocrinol Metab 92:2318-22. 2007
    ..Obligately heterozygous parents are normal. Combined POR and 21-hydroxylase deficiencies have not been reported...
  37. ncbi request reprint Cholesterol binding does not predict activity of the steroidogenic acute regulatory protein, StAR
    Bo Y Baker
    Department of Pediatrics and Metabolic Research Unit, University of California, San Francisco, California 94143, USA
    J Biol Chem 282:10223-32. 2007
    ..These data indicate that cholesterol binding and transfer activities are distinct from its activity to induce steroidogenesis. StAR appears to act by other mechanisms in addition to cholesterol binding...
  38. ncbi request reprint Molecular evolution of adrenarche: structural and functional analysis of p450c17 from four primate species
    Wiebke Arlt
    Department of Pediatrics and the Metabolic Research Unit, University of California, San Francisco, California 94143 0978, USA
    Endocrinology 143:4665-72. 2002
    ..These data establish that Arg255 is important for 17alpha-hydroxylase activity and show that the evolution of adrenarche in higher primates is not determined by variations in the sequence of P450c17...
  39. pmc Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations
    Ningwu Huang
    Departments of Pediatrics and Biopharmaceutical Sciences, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 105:1733-8. 2008
    ..The activity of A503V was reduced to a modest but statistically significant degree in all four assays, suggesting that it may play an important role in interindividual variation in drug response...
  40. pmc Pathways leading to phosphorylation of p450c17 and to the posttranslational regulation of androgen biosynthesis
    Meng Kian Tee
    Department of Pediatrics and the Metabolic Research Unit, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Endocrinology 149:2667-77. 2008
    ..We conclude that members of the ROCK/Rho pathway act upstream from the kinase that phosphorylates P450c17 in a fashion that augments 17,20 lyase activity, possibly acting to catalyze a priming phosphorylation...
  41. doi request reprint Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19
    Vishal Agrawal
    Department of Pediatrics, University of California, San Francisco, California 94143 0978, USA
    Pharmacogenet Genomics 18:569-76. 2008
    ..We examined the effects of POR sequence variants on two drug-metabolizing P450 enzymes, CYP1A2 and CYP2C19...
  42. ncbi request reprint Disorders of androgen biosynthesis
    Walter L Miller
    Department of Pediatrics, The Metabolic Research Unit, Center for Reproductive Sciences, University of California San Francisco, 1466 Fourth Avenue, San Francisco, CA 94143 0978, USA
    Semin Reprod Med 20:205-16. 2002
    ....
  43. pmc Clinical, genetic, and functional characterization of four patients carrying partial loss-of-function mutations in the steroidogenic acute regulatory protein (StAR)
    Taninee Sahakitrungruang
    Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 10330 Bangkok, Thailand corrected
    J Clin Endocrinol Metab 95:3352-9. 2010
    ..Affected individuals can present with a phenotype of late onset adrenal insufficiency with only mild or minimally disordered sexual development...
  44. ncbi request reprint A genetic isolate of congenital lipoid adrenal hyperplasia with atypical clinical findings
    Xin Chen
    Department of Pediatrics, University of California, San Francisco, CA 94143 0978, USA
    J Clin Endocrinol Metab 90:835-40. 2005
    ..Thus, the loss of all assayable activity in vitro correlated poorly with the later onset of clinical symptoms in these patients. Lipoid CAH may present much later in life than previously thought...
  45. ncbi request reprint Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome
    Christa E Flück
    Department of Pediatrics, University of California San Francisco, San Francisco, California 94143 0978, USA
    Nat Genet 36:228-30. 2004
    ..Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion...
  46. doi request reprint The serine phosphorylation hypothesis of polycystic ovary syndrome: a unifying mechanism for hyperandrogenemia and insulin resistance
    Andrew A Bremer
    Department of Pediatrics, Division of Endocrinology, University of California Davis, Sacramento, California 95817 2208, USA
    Fertil Steril 89:1039-48. 2008
    ..Further defining the molecular mechanisms regulating androgen biosynthesis and insulin action in PCOS patients will permit a better understanding of the syndrome and may lead to the generation of novel specific pharmacologic therapies...
  47. ncbi request reprint Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2
    Christa E Flück
    Department of Pediatrics and the Metabolic Research Unit, University of California San Francisco, San Francisco, California, USA
    Epilepsia 46:444-8. 2005
    ..The steroidogenic enzymes 3beta HSDII (3beta-hydroxysteroid dehydrogenase) and P450c17 (17alpha-hydroxylase/17,20 lyase) are essential for C19 steroid biosynthesis, which is enhanced during adrenarche and in PCOS...
  48. pmc Human cytochrome p450c17: single step purification and phosphorylation of serine 258 by protein kinase a
    Yue Hao Wang
    Professor of Pediatrics and Chief of Endocrinology, HSE 1427, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Endocrinology 151:1677-84. 2010
    ..Using our novel vector and a series of mutations, we identified the P450c17 site phosphorylated by PKA as Ser258...
  49. pmc The common P450 oxidoreductase variant A503V is not a modifier gene for 21-hydroxylase deficiency
    Larissa G Gomes
    Department of Pediatrics, HSE 1401, 513 Parnassus Avenue, University of California San Francisco, San Francisco, CA 94143 0978, USA
    J Clin Endocrinol Metab 93:2913-6. 2008
    ..Mutations in P450 oxidoreductase (POR), the protein that transfers electrons from reduced nicotinamide adenine dinucleotide phosphate to all microsomal P450s, can ameliorate the 21OHD phenotype and, therefore, could be a modifier gene...
  50. ncbi request reprint Lack of defects in androgen production in children with hypospadias
    Nicholas M Holmes
    Department of Urology, University of California, San Francisco, California 94143, USA
    J Clin Endocrinol Metab 89:2811-6. 2004
    ..Routine abnormalities in the androgen biosynthetic pathway are an unlikely cause of any degree of hypospadias in boys without accompanying cryptorchidism or genital malformations...
  51. ncbi request reprint Cinnamic acid based thiazolidinediones inhibit human P450c17 and 3beta-hydroxysteroid dehydrogenase and improve insulin sensitivity independent of PPARgamma agonist activity
    Weibke Arlt
    Department of Pediatrics and the Metabolic Research Unit, University of California, San Francisco, California 94143 0978, USA
    J Mol Endocrinol 32:425-36. 2004
    ..The similar glucose-lowering effects of M1 and rosiglitazone, despite their vast differences in PPARgamma agonist activity, suggests these two actions may occur by separate mechanisms...
  52. ncbi request reprint GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1
    Christa E Flück
    Department of Pediatrics, Building MR IV, Room 207, University of California San Francisco, San Francisco, California 94143 0978, USA
    Mol Endocrinol 18:1144-57. 2004
    ..Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells...
  53. ncbi request reprint Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1alpha-hydroxylase gene expression in the proximal renal tubule
    Martin Y H Zhang
    Department of Pediatrics, University of California, San Francisco, California 94143, USA
    Endocrinology 143:587-95. 2002
    ..The increase in P450c1alpha gene expression, which occurs exclusively in the proximal renal tubule, is due at least in part to increased transcription of the P450c1alpha gene...
  54. ncbi request reprint Minireview: regulation of steroidogenesis by electron transfer
    Walter L Miller
    Department of Pediatrics, Building MR 4, Room 209, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Endocrinology 146:2544-50. 2005
    ..Nevertheless, mutation of the human POR gene is compatible with life, causing multiple steroidogenic defects and a skeletal dysplasia called Antley-Bixler syndrome...
  55. ncbi request reprint Near-miss apparent SIDS from adrenal crisis
    Heidi L Gassner
    Department of Pediatrics, University of California, San Francisco, California 94143 0978, USA
    J Pediatr 145:178-83. 2004
    ..We evaluated 3 infants with adrenal crisis who presented at 6 to 8 months of age with near-miss sudden infant death syndrome (SIDS)...
  56. ncbi request reprint pH-dependent Interactions of the carboxyl-terminal helix of steroidogenic acute regulatory protein with synthetic membranes
    Dustin C Yaworsky
    Department of Pediatrics and the Metabolic Research Unit, University of California San Francisco, 94143, USA
    J Biol Chem 280:2045-54. 2005
    ..These results further support StAR undergoing a pH-dependent change in its conformation when interacting with the acidic phospholipid head groups of a membrane...
  57. ncbi request reprint Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of vitamin D 25-hydroxylase
    Chin Jia Lin
    Department of Pediatrics, University of California, San Francisco, CA 94143 0978, USA
    Mol Genet Metab 80:469-72. 2003
    ..25-Hydroxylation occurs in both mitochondria and microsomes. The existence genes encoding distinct enzymes would provide genetic redundancy, explaining the rarity of apparent vitamin D 25-hydroxylase deficiency...
  58. pmc Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the steroidogenic acute regulatory protein with very late presentation and normal male genitalia
    Bo Y Baker
    Department of Pediatrics, University of California, San Francisco, CA 94143, USA
    J Clin Endocrinol Metab 91:4781-5. 2006
    ....
  59. ncbi request reprint Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay
    Christa E Flück
    Department of Pediatrics and Metabolic Research Unit, University of California, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 87:4318-23. 2002
    ..This assay provides excellent sensitivity in an easily assayed transient transfection system, providing a more rapid and efficient measurement of ACTH receptor activity...
  60. doi request reprint Novel P450c17 mutation H373D causing combined 17alpha-hydroxylase/17,20-lyase deficiency
    Taninee Sahakitrungruang
    University of California San Francisco, San Francisco, CA 94143 0978, USA
    J Clin Endocrinol Metab 94:3089-92. 2009
    ..This disorder is caused by defects in P450c17, encoded by the CYP17A1 gene...
  61. pmc High-yield expression of a catalytically active membrane-bound protein: human P450 oxidoreductase
    Duanpen Sandee
    Department of Pediatrics, University of California, HSE 1401, 513 Parnassus Avenue, San Francisco, San Francisco, California 94143 0978, USA
    Endocrinology 152:2904-8. 2011
    ..This expression and purification system permits the rapid preparation of large amounts of highly pure, biologically active POR and may be generally applicable for the preparation of membrane-bound proteins...
  62. pmc Transcriptional regulation of the human P450 oxidoreductase gene: hormonal regulation and influence of promoter polymorphisms
    Meng Kian Tee
    Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143 0978, USA
    Mol Endocrinol 25:715-31. 2011
    ....
  63. pmc Partial defect in the cholesterol side-chain cleavage enzyme P450scc (CYP11A1) resembling nonclassic congenital lipoid adrenal hyperplasia
    Taninee Sahakitrungruang
    Department of Pediatrics, University of California San Francisco, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 96:792-8. 2011
    ..Nonclassic lipoid CAH is a recently recognized disorder caused by mutations in the steroidogenic acute regulatory protein (StAR) that retain partial function...
  64. pmc Extraadrenal 21-hydroxylation by CYP2C19 and CYP3A4: effect on 21-hydroxylase deficiency
    Larissa G Gomes
    Department of Pediatrics, HSE 1401, 513 Parnassus Avenue, University of California, San Francisco, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 94:89-95. 2009
    ..Some hepatic P450 enzymes can 21-hydroxylate progesterone, but their physiological relevance in modifying 21OHD is not known...
  65. ncbi request reprint Dexamethasone does not exert direct intracellular feedback on steroidogenesis in human adrenal NCI-H295A cells
    Andrea Dardis
    Department of Pediatrics and the Metabolic Research Unit, University of California, San Francisco, San Francisco, California 94143 0978, USA
    J Endocrinol 179:131-42. 2003
    ..Because the regulation of steroidogenic processes in NCI-H295A cells closely resembles such regulation in the adrenal, we suggest that Dex may not act by an intra-adrenal mechanism in the experimental prenatal treatment of CAH...
  66. pmc Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc
    Chan Jong Kim
    Department of Pediatrics, University of California San Francisco, San Francisco, California 94143 0978, USA
    J Clin Endocrinol Metab 93:696-702. 2008
    ....
  67. ncbi request reprint Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into leydig cell mitochondria
    Thierry Hauet
    Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20057, USA
    Mol Endocrinol 19:540-54. 2005
    ..These data suggest that both StAR and PBR proteins are indispensable elements of the steroidogenic machinery and function in a coordinated manner to transfer cholesterol into mitochondria...
  68. ncbi request reprint Transfer of cholesterol between phospholipid vesicles mediated by the steroidogenic acute regulatory protein (StAR)
    Robert C Tuckey
    Department of Biochemistry, University of Western Australia, Crawley, Australia
    J Biol Chem 277:47123-8. 2002
    ..Thus StAR can transfer cholesterol between synthetic membranes without other protein components found in mitochondria...
  69. ncbi request reprint Differential regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells: role of SR-B1-mediated selective cholesteryl ester transport
    Rekha M Rao
    Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA
    Biol Reprod 68:114-21. 2003
    ....
  70. ncbi request reprint Formation and functioning of fused cholesterol side-chain cleavage enzymes
    Pavel A Nazarov
    Belozersky Institute of Physico Chemical Biology, Lomonosov Moscow State University, Russia
    DNA Cell Biol 22:243-52. 2003
    ..Thus, the correct folding and catalytic activity of each domain is determined interactively and not independently...
  71. pmc Steroidogenic activity of StAR requires contact with mitochondrial VDAC1 and phosphate carrier protein
    Mahuya Bose
    Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA
    J Biol Chem 283:8837-45. 2008
    ..VDAC1 and phosphate carrier protein are the first OMM proteins shown to contact StAR...
  72. pmc Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency
    Eli Hershkovitz
    Pediatric Endocrinology and Metabolic Unit, Soroka University Medical Center, P O Box 151, Beer Sheva 84101, Israel
    J Clin Endocrinol Metab 93:3584-8. 2008
    ..Most patients with 17,20-lyase deficiency have mutations in the domain of P450c17 that interact with the electron-donating redox partner, P450 oxidoreductase (POR)...
  73. doi request reprint StAR-like activity and molten globule behavior of StARD6, a male germ-line protein
    Himangshu S Bose
    Department of Physiology, University of Florida, Gainesville, Florida 32610, USA
    Biochemistry 47:2277-88. 2008
    ..StARD6, which is expressed only in male germ-line cells, thus exhibits biological and biophysical properties that imply a role in steroidogenesis...
  74. ncbi request reprint Molten globule structure and steroidogenic activity of N-218 MLN64 in human placental mitochondria
    Robert C Tuckey
    Department of Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences, The University of Western Australia, Crawley, Australia
    Endocrinology 145:1700-7. 2004
    ..The results reveal that with saturating MLN64, steroidogenesis by placental mitochondria proceeds at near-maximal rate...
  75. doi request reprint P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia
    Christa E Flück
    Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, University of Bern, Bern, Switzerland
    Endocr Dev 13:67-81. 2008
    ..Thus, the impact of POR mutations on drug metabolism by hepatic P450s requires further investigation...
  76. doi request reprint Genetic and clinical features of p450 oxidoreductase deficiency
    Rachel R Scott
    Division of Endocrinology, Department of Paediatrics, IWK Health Centre, Dalhousie University, Halifax, N S, Canada
    Horm Res 69:266-75. 2008
    ..Given the varied physical and biochemical phenotype of POR deficiency and the risk of adrenal insufficiency, clinicians should be alert to this potential diagnosis...
  77. ncbi request reprint P450 oxidoreductase deficiency
    Walter L Miller
    Lancet 364:1663. 2004
  78. ncbi request reprint Vitamin D 25-hydroxylase deficiency
    Qing Dong
    Mol Genet Metab 83:197-8. 2004
  79. ncbi request reprint Steroid 17alpha-hydroxylase deficiency--not rare everywhere
    Walter L Miller
    J Clin Endocrinol Metab 89:40-2. 2004
  80. ncbi request reprint Consensus statement on 21-hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society
    Peter E Clayton
    Horm Res 58:188-95. 2002
  81. ncbi request reprint P450 oxidoreductase deficiency: a new form of congenital adrenal hyperplasia
    Christa E Flück
    Pediatric Endocrinology and Diabetology, University Children s Hospital Bern, Bern, Switzerland
    Curr Opin Pediatr 18:435-41. 2006
    ..We review current knowledge of P450 oxidoreductase deficiency and its broader implications...

Research Grants38

  1. Molecular Biology of Steroidogenic Proteins
    WALTER MILLER; Fiscal Year: 2005
    ..Fulfilling these 5 aims will substantially advance our understanding of the mechanism of StAR's action. ..
  2. ANDROGEN PRODUCTION IN ADRENARCHE AND PCOS
    WALTER MILLER; Fiscal Year: 2006
    ..abstract_text> ..
  3. Pharmacogenomics of Human P450 Oxidoreductase
    WALTER MILLER; Fiscal Year: 2007
    ..Successful completion of these aims will substantially increase knowledge about the genetic factors leading to variations in drug response. ..
  4. TRAINING GRANT IN PEDIATRIC ENDOCRINOLOGY
    WALTER MILLER; Fiscal Year: 2007
    ..The continuing success of this program is shown by the fact that since 1966, 77% of the 153 trainees in this program have remained in academic medicine. ..
  5. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 2007
    ..Fulfilling these aims will substantially advance our understanding of this indispensable initial step in the production of all adrenal and gonadal steroid hormones. ..
  6. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 2009
    ..Fulfilling these aims will substantially advance our understanding of this indispensable initial step in the production of all adrenal and gonadal steroid hormones. ..
  7. Pharmacogenomics of Human P450 Oxidoreductase
    WALTER MILLER; Fiscal Year: 2009
    ..This project explores a third possibility, a gene called POR, that is needed for the activity of drug-metabolizing enzymes. ..
  8. Pharmacogenomics of Human P450 Oxidoreductase
    WALTER MILLER; Fiscal Year: 2009
    ..Successful completion of these aims will substantially increase knowledge about the genetic factors leading to variations in drug response. ..
  9. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    Walter L Miller; Fiscal Year: 2010
    ..Fulfilling these aims will substantially advance our understanding of this indispensable initial step in the production of all adrenal and gonadal steroid hormones. ..
  10. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 1990
  11. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 1993
    ..Successful completion of this work will greatly expand our understanding of the roles of these newly discovered genes in adrenal function...
  12. MOLECULAR BIOLOGY OF STEROIDOGENIC P450 ENZYMES
    WALTER MILLER; Fiscal Year: 2001
    ..An Aim in the previous submission on genetics of hypertension has been deleted. ..
  13. Pharmacogenomics of Human P450 Oxidoreductase
    Walter L Miller; Fiscal Year: 2010
    ..This project explores a third possibility, a gene called POR, that is needed for the activity of drug-metabolizing enzymes. ..