Cell cycle-dependent regulation of extra-adrenal glucocorticoid synthesis in murine intestinal epithelial cells

Autor: Mario Noti, Dominic Leiser, Atanas G. Atanasov, Kristina Schoonjans, Nadia Corazza, Corinne Roesselet, Thomas Brunner
Přispěvatelé: Division of Immunopathology, University of Bern, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Peney, Maité, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2008
Předmět:
steroidogenesis
MESH: Cyclin D1
Cellular differentiation
Cell
nuclear receptors
Receptors
Cytoplasmic and Nuclear
Endogeny
MESH: Cell Cycle
Biochemistry
Retinoblastoma Protein
MESH: Cholesterol Side-Chain Cleavage Enzyme
Mice
0302 clinical medicine
Cyclin D1
MESH: Animals
Intestinal Mucosa
Receptor
0303 health sciences
Nocodazole
Cell Cycle
Cell Differentiation
Transfection
Cell cycle
MESH: CDC2 Protein Kinase
Cell biology
medicine.anatomical_structure
MESH: Kinetin
030220 oncology & carcinogenesis
MESH: Intestinal Mucosa
MESH: Forskolin
Biotechnology
MESH: Cell Differentiation
MESH: Aphidicolin
Biology
Cyclin B
MESH: Receptors
Cytoplasmic and Nuclear
MESH: Nocodazole
Cell Line
03 medical and health sciences
MESH: Doxorubicin
Aphidicolin
mucosal immunology
ddc:570
CDC2 Protein Kinase
Genetics
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Cholesterol Side-Chain Cleavage Enzyme
Cyclin B1
Molecular Biology
Glucocorticoids
MESH: Mice
030304 developmental biology
MESH: Transfection
Colforsin
MESH: Cyclin B
Kinetin
MESH: Retinoblastoma Protein
MESH: Cell Line
Nuclear receptor
Cell culture
Doxorubicin
liver receptor homologue-1
Steroid 11-beta-Hydroxylase
MESH: Glucocorticoids
MESH: Steroid 11-beta-Hydroxylase
Zdroj: FASEB Journal
FASEB Journal, Federation of American Society of Experimental Biology, 2008, 22 (12), pp.4117-25. ⟨10.1096/fj.08-114157⟩
FASEB Journal, 2008, 22 (12), pp.4117-25. ⟨10.1096/fj.08-114157⟩
ISSN: 0892-6638
1530-6860
DOI: 10.1096/fj.08-114157⟩
Popis: International audience; Glucocorticoids are anti-inflammatory steroids with important applications in the treatment of inflammatory diseases. Endogenous glucocorticoids are mainly produced by the adrenal glands, although there is increasing evidence for extra-adrenal sources. Recent findings show that intestinal crypt cells produce glucocorticoids, which contribute to the maintenance of intestinal immune homeostasis. Intestinal glucocorticoid synthesis is critically regulated by the transcription factor liver receptor homologue-1 (LRH-1). As expression of steroidogenic enzymes and LRH-1 is restricted to the proliferating cells of the crypts, we aimed to investigate the role of the cell cycle in the regulation of LRH-1 activity and intestinal glucocorticoid synthesis. We here show that either pharmacological or molecular modulation of cell cycle progression significantly inhibited expression of steroidogenic enzymes and synthesis of glucocorticoids in intestinal epithelial cells. Synchronization of intestinal epithelial cells in the cell cycle revealed that expression of steroidogenic enzymes is preferentially induced at the G(1)/S stage. Differentiation of immature intestinal epithelial cells to mature nonproliferating cells also resulted in reduced expression of steroidogenic enzymes. This cell cycle-related effect on intestinal steroidogenesis was found to be mediated through the regulation of LRH-1 transcriptional activity. This mechanism may restrict intestinal glucocorticoid synthesis to the proliferating cells of the crypts.
Databáze: OpenAIRE
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