Research Topics
Genomes and Genes
| S H MellonSummaryAffiliation: University of California Country: USA Publications
Research Grants
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Detail Information
Publications
Expression of P450c17 in the human fetal nervous systemMarcus 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...- Neurosteroid regulation of central nervous system developmentSynthia 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)... - Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C diseaseSynthia 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... 
Translin coactivates steroidogenic factor-1-stimulated transcriptionSynthia 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...- Synthesis, regulation, and function of neurosteroidsSynthia 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 - Neurosteroids: biochemistry and clinical significanceSynthia 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... - Biosynthesis and action of neurosteroidsS 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.... - Transcriptional regulation of P450scc gene expression in neural and steroidogenic cells: implications for regulation of neurosteroidogenesisP 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... - Ku autoimmune antigen is involved in placental regulation of rat P450c17 gene transcriptionP 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... - Novel role for the nuclear phosphoprotein SET in transcriptional activation of P450c17 and initiation of neurosteroidogenesisN 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... - 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 activitiesS 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... - Orphan receptors, proto-oncogenes and other nuclear factors regulate P450C17 gene transcriptionS 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.... - Biosynthesis of the neurosteroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha hp), a specific inhibitor of FSH releaseL 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... - 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.... - 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 activitiesC 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... - DNA sequence-dependent regulation of SF-1-mediated transcriptionPaul 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... - Expression of the steroidogenic enzyme P450scc in the central and peripheral nervous systems during rodent embryogenesisN A Compagnone
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143 0556, USA
Endocrinology 136:2689-96. 1995.... - Expression of steroid sulfatase during embryogenesisN 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... - Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brainS 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... - Regulation of uterine gamma-aminobutyric acid(A) receptor subunit expression throughout pregnancyE 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... - Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21BJ 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... - Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymesL 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... 
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?..- Of sound mind and body: depression, disease, and accelerated agingOwen 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... - 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.... - Biosynthesis of neurosteroids and regulation of their synthesisS 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.... - Polyribonucleotide phosphorylase is a double-stranded DNA-binding proteinP 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... - Transcriptional regulation of P450scc gene expression in the embryonic rodent nervous systemFabian 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... - Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorderWilliam 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... - Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous systemN A Compagnone
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143, USA
Endocrinology 136:5212-23. 1995.... - Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanoloneLisa 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... - 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... - cAMP regulates P450scc gene expression by a cycloheximide-insensitive mechanism in cultured mouse Leydig MA-10 cellsS 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... - Regulation of P450c17 expression in the early embryo depends on GATA factorsYimin Shi
Department of Obstetrics, Gynecology, and Reproductive Science, University of California San Francisco, San Francisco, CA 94143 0556, USA
Endocrinology 150:946-56. 2009.... - Expression and regulation of adrenodoxin and P450scc mRNA in rodent tissuesS H Mellon
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco 94143 0556
DNA Cell Biol 10:339-47. 1991.... - Deletion of the mouse P450c17 gene causes early embryonic lethalitySusanna 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... - Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17Amit 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... - Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1alpha-hydroxylase gene expression in the proximal renal tubuleMartin 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... - Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alphaCheol 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... - Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C diseaseS 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 Grants
- Neurosteroids in health and diseaseSynthia 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. ..
- Integrated Training in Reproductive SciencesSynthia Mellon; Fiscal Year: 2007....
- REGULATION OF REPRODUCTIONSynthia Mellon; Fiscal Year: 2005..abstract_text> ..
- REGULATION OF REPRODUCTIONSynthia 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. ..
- REGULATION OF REPRODUCTIONSynthia 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...