ArticleJournal of molecular endocrinology2014
p38 MAPK regulates steroidogenesis through transcriptional repression of STAR gene.
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Article in Journal of molecular endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
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18 citing papers in PubMed, 34 citations in OpenAlex.
- Lycopene Alleviates T-2 Toxin-Induced Testosterone Synthesis Disorder by Inhibiting ROS/p38/TORC2/CREB Axis.Antioxidants (Basel, Switzerland) · 2026Article
- Oxidative Stress-induced Hormonal Disruption in Male Reproduction.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Thromboxane AAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Evaluation of the Expression and Localization of the Multifunctional Protein CacyBP/SIP and Elements of the MAPK Signaling Pathway in the Adrenal Glands of Rats with Primary and Secondary Hypertension.International journal of molecular sciences · 2023Article
- Seasonal Change in Adiponectin Associated with Ovarian Morphology and Function in Wild Ground Squirrels (International journal of molecular sciences · 2022Article
- Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1.Acta pharmacologica Sinica · 2022Article
- Mechanism of Inflammatory Associated Impairment of Sperm Function, Spermatogenesis and Steroidogenesis.Frontiers in endocrinology · 2022Review
- Role of p38 MAPK Signalling in Testis Development and Male Fertility.Oxidative medicine and cellular longevity · 2022Review
- The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease.Antioxidants (Basel, Switzerland) · 2021Review
- BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway.Frontiers in cell and developmental biology · 2021Article
- SOD2 deficiency-induced oxidative stress attenuates steroidogenesis in mouse ovarian granulosa cells.Molecular and cellular endocrinology · 2021Article
- Kinobead/LC-MS Phosphokinome Profiling Enables Rapid Analyses of Kinase-Dependent Cell Signaling Networks.Journal of proteome research · 2020Article
- Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH.Molecular and cellular endocrinology · 2020Article
- Article
- Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells.Frontiers in endocrinology · 2019Article
- Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.Journal of the Endocrine Society · 2018Article
- Steroidogenesis in Leydig cells: effects of aging and environmental factors.Reproduction (Cambridge, England) · 2017Review
- Feedback inhibition of CREB signaling by p38 MAPK contributes to the negative regulation of steroidogenesis.Reproductive biology and endocrinology : RB&E · 2017Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Syed Kashif ZaidiGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USAGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Wen-Jun ShenGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USAGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Stefanie BittnerGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Alex BittnerGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Mark P McLeanGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Jiahuai HanGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Roger J DavisGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Fredric B KraemerGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USAGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Salman AzharGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USAGeriatric ResearchEducation and Clinical Center (GRECC-182B), VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USADivision of EndocrinologyDivision of Gastroenterology and HepatologyStanford University, Stanford, California 94305, USADepartment of Obstetrics and GynecologyUniversity of South Florida College of Medicine, Tampa, Florida 33612, USAState Key Laboratory of Cellular Stress BiologySchool of Life Sciences, Xiamen University, Xiamen, Fujian 361005, ChinaProgram in Molecular MedicineUniversity of Massachusetts Medical School, Worcester, Massachusetts 01605, USA salman.azhar@va.gov.
VA Palo Alto Health Care System · USXiamen University · CN
Funding
HOW DO CELLS PROCESS HIGH DENSITY LIPOPROTEINS?R01HL033881 · NHLBI · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI AZHAR, SALMAN · 1985 to 2014
$3.8MHypo-Lipidemic Actions of Creosote Bush-Derived NDGAR01HL092473 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI AZHAR, SALMAN · 2009 to 2013
$1.8MLipolysisI01BX000398 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI KRAEMER, FREDRIC B. · 2009 to 2020
–Role of Cholesterol in Age-related Decline in SteroidogenesisI01BX001923 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI AZHAR, SALMAN · 2013 to 2020
–BLRD VA I01 BX000398BLRD VA I01 BX001923NHLBI NIH HHS 1R01HL92473NHLBI NIH HHS 2R01HL33881NHLBI NIH HHS R01 HL033881NHLBI NIH HHS R01 HL092473
Abstract
STAR/StarD1, part of a protein complex, mediates the transport of cholesterol from the outer to inner mitochondrial membrane, which is the rate-limiting step for steroidogenesis, and where steroid hormone synthesis begins. Herein, we examined the role of oxidant-sensitive p38 MAPKs in the regulation of STAR gene transcription, using model steroidogenic cell lines. Our data indicate that oxidant activation of p38 MAPK exhibits a negative regulatory role in the induction of functional expression of STAR, as evidenced by enhanced induction of STAR (mRNA/protein) expression and increased steroidogenesis during pharmacological inhibition of p38 MAPK or in cells with increased transient overexpression of a dominant-negative (dn) form of p38 MAPKα or p38 MAPKβ. Studies with rat Star-promoter demonstrated that overexpression of p38 MAPKα-wt, -β, or -γ significantly reduced both basal and cAMP-sensitive promoter activity. In contrast, overexpression of p38 MAPKα-dn, -β, or -γ enhanced the Star promoter activity under basal conditions and in response to cAMP stimulation. Use of various constitutively active and dn constructs and designer knock-out cell lines demonstrated that MKK3 and MKK6, the upstream activators of p38 MAPKs, play a role in p38 MAPKα-mediated inhibition of Star promoter activity. In addition, our studies raised the possibility of CREB being a potential target of the p38 MAPK inhibitory effect on Star promoter activity. Collectively, these data provide novel mechanistic information about how oxidant-sensitive p38 MAPKs, particularly p38 MAPKα, contribute to the negative regulation of Star gene expression and inhibit steroidogenesis.
Indexed as
AnimalsBucladesineCell LineCells, CulturedCyclic AMP Response Element-Binding ProteinHEK293 CellsHumansIsoenzymesMAP Kinase Kinase 3MAP Kinase Kinase 6MiceMice, KnockoutOxidantsp38 Mitogen-Activated Protein KinasesPhosphoproteinsProgesteroneBucladesineCreb1 protein, mouseCyclic AMP Response Element-Binding ProteinIsoenzymesMap2k3 protein, mouseMap2k6 protein, mouseMAP Kinase Kinase 3MAP Kinase Kinase 6Oxidantsp38 Mitogen-Activated Protein KinasesPhosphoproteinsProgesteroneRNA, MessengerSteroidogenic Acute Regulatory ProteinSteroidscAMPCREBMLTC-1 cellsoxidative stresssteroid hormonessteroidsY1 cells
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