S H Mellon

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Expression of P450c17 in the human fetal nervous system
    Marcus D Schonemann
    Department of Obstetrics, Gynecology, and Reproductive Science, University of California, San Francisco, 513 Parnassus Avenue, Box 0556, San Francisco, California 94143 0556, USA
    Endocrinology 153:2494-505. 2012
  2. pmc Neurosteroid regulation of central nervous system development
    Synthia H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California San Francisco, Box 0556, San Francisco, CA 94143 0556, USA
    Pharmacol Ther 116:107-24. 2007
  3. pmc Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease
    Synthia H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA
    Brain Res Rev 57:410-20. 2008
  4. ncbi request reprint Translin coactivates steroidogenic factor-1-stimulated transcription
    Synthia H Mellon
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143 0556, USA
    Mol Endocrinol 21:89-105. 2007
  5. ncbi request reprint Synthesis, regulation, and function of neurosteroids
    Synthia H Mellon
    Dept of Obstetrics and Gynecology, University of California, San Francisco, 513 Parnassus Ave, San Francisco, CA 94143, USA
    Endocr Res 28:463. 2002
  6. ncbi request reprint Neurosteroids: biochemistry and clinical significance
    Synthia H Mellon
    Dept of Obstetrics, Gynecology and Reproductive Sciences, 513 Parnassus Ave, Box 0556, San Francisco, CA 94143 0556, USA
    Trends Endocrinol Metab 13:35-43. 2002
  7. ncbi request reprint Biosynthesis and action of neurosteroids
    S H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Center for Reproductive Sciences, The Metabolic Research Unit, University of California, San Francisco, CA 94143, USA
    Brain Res Brain Res Rev 37:3-12. 2001
  8. ncbi request reprint Transcriptional regulation of P450scc gene expression in neural and steroidogenic cells: implications for regulation of neurosteroidogenesis
    P Zhang
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143, USA
    Mol Endocrinol 9:1571-82. 1995
  9. ncbi request reprint Ku autoimmune antigen is involved in placental regulation of rat P450c17 gene transcription
    P Zhang
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Reproductive Endocrinology Center, University of California, San Francisco 94143 0556, USA
    DNA Cell Biol 18:197-208. 1999
  10. ncbi request reprint Novel role for the nuclear phosphoprotein SET in transcriptional activation of P450c17 and initiation of neurosteroidogenesis
    N A Compagnone
    Center for Reproductive Sciences, Department of Obstetrics and Gynecology and Reproductive Sciences, University of California San Francisco 94143 0556, USA
    Mol Endocrinol 14:875-88. 2000

Research Grants

  1. Neurosteroids in health and disease
    Synthia Mellon; Fiscal Year: 2007
  2. Integrated Training in Reproductive Sciences
    Synthia Mellon; Fiscal Year: 2007
  3. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 2005
  4. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 2000
  5. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 1993

Collaborators

Detail Information

Publications40

  1. pmc Expression of P450c17 in the human fetal nervous system
    Marcus D Schonemann
    Department of Obstetrics, Gynecology, and Reproductive Science, University of California, San Francisco, 513 Parnassus Avenue, Box 0556, San Francisco, California 94143 0556, USA
    Endocrinology 153:2494-505. 2012
    ..The expression of P450c17 in structures lacking POR means that P450c17 may not be steroidogenic in those locations, suggesting that P450c17 may have additional functions that do not require POR...
  2. pmc Neurosteroid regulation of central nervous system development
    Synthia H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California San Francisco, Box 0556, San Francisco, CA 94143 0556, USA
    Pharmacol Ther 116:107-24. 2007
    ..This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of 4 distinct neurosteroids: pregnenolone, progesterone, allopregnanolone, and dehydroepiandrosterone (DHEA)...
  3. pmc Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease
    Synthia H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA
    Brain Res Rev 57:410-20. 2008
    ..These animal models further establish the wide range of functions of these compounds, which may ultimately be useful for treatment of human diseases...
  4. ncbi request reprint Translin coactivates steroidogenic factor-1-stimulated transcription
    Synthia H Mellon
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143 0556, USA
    Mol Endocrinol 21:89-105. 2007
    ..Thus, we have identified a new factor that works together with SF-1 to augment gene transcription in a DNA-specific fashion...
  5. ncbi request reprint Synthesis, regulation, and function of neurosteroids
    Synthia H Mellon
    Dept of Obstetrics and Gynecology, University of California, San Francisco, 513 Parnassus Ave, San Francisco, CA 94143, USA
    Endocr Res 28:463. 2002
  6. ncbi request reprint Neurosteroids: biochemistry and clinical significance
    Synthia H Mellon
    Dept of Obstetrics, Gynecology and Reproductive Sciences, 513 Parnassus Ave, Box 0556, San Francisco, CA 94143 0556, USA
    Trends Endocrinol Metab 13:35-43. 2002
    ..The physiological relevance and potential uses of neurosteroids in certain human diseases are discussed...
  7. ncbi request reprint Biosynthesis and action of neurosteroids
    S H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Center for Reproductive Sciences, The Metabolic Research Unit, University of California, San Francisco, CA 94143, USA
    Brain Res Brain Res Rev 37:3-12. 2001
    ....
  8. ncbi request reprint Transcriptional regulation of P450scc gene expression in neural and steroidogenic cells: implications for regulation of neurosteroidogenesis
    P Zhang
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143, USA
    Mol Endocrinol 9:1571-82. 1995
    ..The results further suggest that steroidogenic factor-1 is not involved in regulating neurosteroidogenesis...
  9. ncbi request reprint Ku autoimmune antigen is involved in placental regulation of rat P450c17 gene transcription
    P Zhang
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Reproductive Endocrinology Center, University of California, San Francisco 94143 0556, USA
    DNA Cell Biol 18:197-208. 1999
    ..These data demonstrate a role of Ku in regulating P450c17 gene expression. These data further indicate that although human P450c17 is not normally expressed in the placenta, factors that could activate this gene are indeed present...
  10. ncbi request reprint Novel role for the nuclear phosphoprotein SET in transcriptional activation of P450c17 and initiation of neurosteroidogenesis
    N A Compagnone
    Center for Reproductive Sciences, Department of Obstetrics and Gynecology and Reproductive Sciences, University of California San Francisco 94143 0556, USA
    Mol Endocrinol 14:875-88. 2000
    ..These studies delineate an important new factor in the transcriptional regulation of P450c17 and consequently, in the production of DHEA and sex steroids...
  11. ncbi request reprint P450c11B3 mRNA, transcribed from a third P450c11 gene, is expressed in a tissue-specific, developmentally, and hormonally regulated fashion in the rodent adrenal and encodes a protein with both 11-hydroxylase and 18-hydroxylase activities
    S H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143 0556
    J Biol Chem 270:1643-9. 1995
    ..Thus, P450c11B3 catalyzes 11 beta- and 18-hydroxylation and thus has a spectrum of activities midway between P450c11 beta and P450c11AS...
  12. ncbi request reprint Orphan receptors, proto-oncogenes and other nuclear factors regulate P450C17 gene transcription
    S H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Reproductive Endocrinology Center, University of California, San Francisco, USA
    Endocr Res 24:505-13. 1998
    ....
  13. ncbi request reprint Biosynthesis of the neurosteroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha hp), a specific inhibitor of FSH release
    L D Griffin
    Department of Neurology, University of California, San Francisco, California 94143, USA
    Endocrinology 142:4617-22. 2001
    ..Furthermore, the data suggest that the pituitary has the capacity for 3 alpha HP production, which may provide an additional mechanism for regulation of GnRH action...
  14. ncbi request reprint Developmental gonadal expression of the transcription factor SET and its target gene, P450c17 (17alpha-hydroxylase/c17,20 lyase)
    P Zhang
    Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Reproductive Sciences, and The Metabolic Research Unit, University of California, San Francisco 94143-0556, USA
    DNA Cell Biol 20:613-24. 2001
    ....
  15. ncbi request reprint Transcriptional regulation of rat cytochrome P450c17 expression in mouse Leydig MA-10 and adrenal Y-1 cells: identification of a single protein that mediates both basal and cAMP-induced activities
    C R Givens
    Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143 0556, USA
    DNA Cell Biol 13:1087-98. 1994
    ..Southwestern analysis suggests that one of these proteins is larger than SF-1. This study suggests that a protein that binds to an SF-1 like sequence regulates both basal and cAMP-stimulated rat P450c17 gene expression in rodent cells...
  16. ncbi request reprint DNA sequence-dependent regulation of SF-1-mediated transcription
    Paul B Brake
    Department of Obstetrics, Gynecology, and Reproductive Sciences, The Center for Reproductive Sciences, University of California, San Francisco, California 94143, USA
    DNA Cell Biol 24:148-60. 2005
    ..These data suggest that the mechanism by which SF-1 stimulates transcription is DNA sequence dependent, and may require additional proteins, such as StF-IT-2, for activation at specific regions of DNA...
  17. ncbi request reprint Expression of the steroidogenic enzyme P450scc in the central and peripheral nervous systems during rodent embryogenesis
    N A Compagnone
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143 0556, USA
    Endocrinology 136:2689-96. 1995
    ....
  18. ncbi request reprint Expression of steroid sulfatase during embryogenesis
    N A Compagnone
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143, USA
    Endocrinology 138:4768-73. 1997
    ..The sites of expression of STS were similar to those of P450c17, suggesting that these two enzymes may have concerted actions in similar functional processes...
  19. ncbi request reprint Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain
    S H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco 94143 0556
    Brain Res 629:283-92. 1993
    ..Neurosteroids may be derivatives of known classic steroids, and/or may function through non-classic steroid hormone receptors, such as GABAA, N-methyl-D-aspartate, and corticosterone receptors...
  20. ncbi request reprint Regulation of uterine gamma-aminobutyric acid(A) receptor subunit expression throughout pregnancy
    E Fujii
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, California 94143, USA
    Endocrinology 142:1770-7. 2001
    ..These changes may also affect the sensitivity of the GABA(A) receptor to allopregnanolone and thus contribute to the regulation of parturition...
  21. pmc Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B
    J Bristow
    Department of Pediatrics, University of California, San Francisco
    J Cell Biol 122:265-78. 1993
    ..Genetic data suggest that TN-X may be essential for life...
  22. pmc Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes
    L D Griffin
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, Box 0556, San Francisco, CA 94143 0556, USA
    Proc Natl Acad Sci U S A 96:13512-7. 1999
    ..Our results may thus help explain the rapid alleviation of the anxiety and dysphoria associated with late luteal phase dysphoria disorder and major unipolar depression by these SSRIs...
  23. doi request reprint Is serum brain-derived neurotrophic factor a biomarker for cognitive enhancement in schizophrenia?
    Sophia Vinogradov
    Department of Psychiatry, School of Medicine, University of California San Francisco, California 94121, USA
    Biol Psychiatry 66:549-53. 2009
    ..We asked: would neuroplasticity-based cognitive training in schizophrenia result in increased serum BDNF?..
  24. pmc Of sound mind and body: depression, disease, and accelerated aging
    Owen M Wolkowitz
    Department of Psychiatry, School of Medicine, University of California, San Francisco, California, USA
    Dialogues Clin Neurosci 13:25-39. 2011
    ..These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators...
  25. doi request reprint Depression gets old fast: do stress and depression accelerate cell aging?
    Owen M Wolkowitz
    Department of Psychiatry, University of California School of Medicine, San Francisco, California, USA
    Depress Anxiety 27:327-38. 2010
    ....
  26. ncbi request reprint Biosynthesis of neurosteroids and regulation of their synthesis
    S H Mellon
    Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, Metabolic Research Unit, University of California-San Francisco, San Francisco, California 94143-0556, USA
    Int Rev Neurobiol 46:33-78. 2001
    ....
  27. ncbi request reprint Polyribonucleotide phosphorylase is a double-stranded DNA-binding protein
    P Zhang
    Department of Obstetrics, Gynecology and Reproductive Sciences, The Reproductive Endocrinology Center, University of California, San Francisco 94143 0556, USA
    DNA Cell Biol 17:169-75. 1998
    ..Our data further demonstrate that PNPase binds to DNA in a sequence-specific manner. These data suggest that PNPase may have previously unappreciated DNA-related functions in addition to its known role in mRNA degradation...
  28. ncbi request reprint Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous system
    Fabian Hammer
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue, Box 0556, San Francisco, CA 94143 0556, USA
    Endocrinology 145:901-12. 2004
    ..Thus, members of the Sp transcription family play a role in activating P450scc gene transcription in the nervous system, and Ku may further augment this activation...
  29. pmc Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorder
    William Berger
    Department of Psychiatry, University of California, San Francisco, CA, USA
    Prog Neuropsychopharmacol Biol Psychiatry 34:1279-84. 2010
    ..Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats...
  30. ncbi request reprint Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system
    N A Compagnone
    Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143, USA
    Endocrinology 136:5212-23. 1995
    ....
  31. ncbi request reprint Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone
    Lisa D Griffin
    Department of Neurology, Center for Reproductive Sciences, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0556, USA
    Nat Med 10:704-11. 2004
    ..Earlier administration increases effectiveness of treatment. Decreased production of allopregnanolone apparently contributes to the pathology of NP-C; thus, neurosteroid treatment may be useful in ameliorating progression of the disease...
  32. pmc Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)
    Nicole Maninger
    Department of Psychiatry, University of California San Francisco, School of Medicine, San Francisco 94143, USA
    Front Neuroendocrinol 30:65-91. 2009
    ..Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed...
  33. pmc cAMP regulates P450scc gene expression by a cycloheximide-insensitive mechanism in cultured mouse Leydig MA-10 cells
    S H Mellon
    Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco 94143
    Proc Natl Acad Sci U S A 86:7775-9. 1989
    ..Similarly, HPLC detected no 17 alpha-hydroxyprogesterone or testosterone synthesis in MA-10 cells. Thus MA-10 cells, unlike untransformed Leydig cells, do not express detectable amounts of P450c17 mRNA or P450c17 activity...
  34. pmc Regulation of P450c17 expression in the early embryo depends on GATA factors
    Yimin Shi
    Department of Obstetrics, Gynecology, and Reproductive Science, University of California San Francisco, San Francisco, CA 94143 0556, USA
    Endocrinology 150:946-56. 2009
    ....
  35. ncbi request reprint Expression and regulation of adrenodoxin and P450scc mRNA in rodent tissues
    S H Mellon
    Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco 94143 0556
    DNA Cell Biol 10:339-47. 1991
    ....
  36. pmc Deletion of the mouse P450c17 gene causes early embryonic lethality
    Susanna R Bair
    Department of Obstetrics, Gynecology, and Reproductive Sciences, The Center for Reproductive Sciences, and The Metabolic Research Unit, University of California, San Francisco, 94143, USA
    Mol Cell Biol 24:5383-90. 2004
    ..These data suggest that steroid products of P450c17 have heretofore-unknown essential functions in early embryonic mouse development...
  37. 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...
  38. 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...
  39. pmc Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alpha
    Cheol Yi Hong
    Hormone Research Center, School of Biological Sciences and Technology, Department of Biology, Chonnam National University, Gwangju 500 757, Republic of Korea
    Mol Cell Biol 24:2593-604. 2004
    ..These findings provide a molecular mechanism underlying the inhibition of testicular steroidogenesis by proinflammatory cytokines...
  40. pmc Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C disease
    S Joshua Langmade
    Center for Cardiovascular Research, Department of Internal Medicine, and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 103:13807-12. 2006
    ..These findings suggest that treatment with pregnane X receptor ligands may be useful clinically in delaying the progressive neurodegeneration in human NPC disease...

Research Grants17

  1. Neurosteroids in health and disease
    Synthia Mellon; Fiscal Year: 2007
    ..Thus this proposal is directed toward the treatment of a broad group of disorders with a novel class of drugs, with NP-C as the model disease. ..
  2. Integrated Training in Reproductive Sciences
    Synthia Mellon; Fiscal Year: 2007
    ....
  3. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 2005
    ..abstract_text> ..
  4. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 2000
    ..In Specific Aim 2, they will clone these factors. In Specific Aim 3, the investigators will explore the role of SF-1 phosphorylation in mediating cAMP and/or basal P450c17 gene expression. ..
  5. REGULATION OF REPRODUCTION
    Synthia Mellon; Fiscal Year: 1993
    ..Successful completion of these studies will give us a better understanding of how adrenals and testes, using the same genes, synthesize different classes of steroid hormones...