Insulin-like growth factor-I activates extracellularly regulated kinase to regulate the p450 side-chain cleavage insulin-like response element in granulosa cells

Autor: Jie Jiang, Yvonne H. Bodenburg, Randall J. Urban, Larry Denner, Gilles Pagès
Přispěvatelé: Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
MAPK/ERK pathway
Swine
Response element
MESH: Insulin-Like Growth Factor I
MESH: Cholesterol Side-Chain Cleavage Enzyme
Mice
0302 clinical medicine
Endocrinology
Gene expression
MESH: Animals
Enzyme Inhibitors
Insulin-Like Growth Factor I
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
MESH: Swine
MESH: Extracellular Signal-Regulated MAP Kinases
[SDV.BDD]Life Sciences [q-bio]/Development Biology
MESH: Chromatin Immunoprecipitation
0303 health sciences
RNA-Binding Proteins
MESH: Nitriles
MESH: Enzyme Inhibitors
Female
MESH: Response Elements
Signal transduction
Chromatin Immunoprecipitation
medicine.medical_specialty
endocrine system
MESH: Enzyme Activation
Sp1 Transcription Factor
Blotting
Western
030209 endocrinology & metabolism
Biology
Response Elements
Article
Cell Line
MESH: Butadienes
03 medical and health sciences
Enzyme activator
Internal medicine
Nitriles
Butadienes
medicine
Animals
Humans
Immunoprecipitation
MESH: Blotting
Western
Cholesterol Side-Chain Cleavage Enzyme
PTB-Associated Splicing Factor
MESH: Mice
030304 developmental biology
MESH: Sp1 Transcription Factor
Reporter gene
Granulosa Cells
MESH: Humans
MESH: Phosphorylation
Activator (genetics)
MESH: Immunoprecipitation
MESH: Granulosa Cells
Molecular biology
MESH: Cell Line
Enzyme Activation
MESH: RNA-Binding Proteins
MESH: Female
Zdroj: Endocrinology
Endocrinology, Endocrine Society, 2010, 151 (6), pp.2819-25. ⟨10.1210/en.2009-1439⟩
ISSN: 0013-7227
DOI: 10.1210/en.2009-1439⟩
Popis: International audience; IGF regulates steroidogenesis in granulosa cells through expression of the cytochrome P450 side-chain cleavage enzyme (P450scc) (CYP11A1), the rate-limiting enzyme in this biosynthetic process. We showed previously that the polypyrimidine tract-binding protein-associated splicing factor (PSF) acts as a repressor, whereas Sp1 is an activator, of P450 gene expression. The aim of the present study was to investigate IGF-stimulated ERK signaling regulating P450scc gene expression in the immortalized porcine granulosa cell line JC-410. We used a reporter gene under control of the IGF response element from the P450scc promoter. Inhibition of ERK phosphorylation with U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene] blocked IGF-I induction of IGF response element reporter gene activity. Western blotting revealed that IGF-I treatment resulted in phosphorylation of ERK that was specifically inhibited by U0126. ERK activation led to phosphorylation of T739 (an ERK site) on Sp1 that was diminished by U0126 or overexpression of PSF. Coimmunoprecipitation and Western blotting of nuclear extracts showed that phosphorylated ERK (pERK) bound PSF under basal conditions. IGF-I caused dissociation of pERK from PSF. Finally, chromatin immunoprecipitation analysis showed that PSF and Sp1 constitutively occupy the P450scc promoter independent of IGF-I treatment. These events provide a potential molecular mechanism for release of PSF repression of P450scc expression by dissociation of pERK and subsequent pERK-mediated phosphorylation of Sp1 to drive transcriptional induction of the P450scc gene in the absence of altered binding of PSF or Sp1 to the promoter. Understanding IGF-I regulation of these critical ovarian signaling pathways is the first step to delineating ovarian hyperstimulation syndromes such as polycystic ovarian syndrome.
Databáze: OpenAIRE
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