Pituitary Corticotroph SOCS-3: Novel Intracellular Regulation of Leukemia-Inhibitory Factor-Mediated Proopiomelanocortin Gene Expression and Adrenocorticotropin Secretion

Autor: Vera Chesnokova, Corinne Bousquet, Shlomo Melmed, Christoph J. Auernhammer
Rok vydání: 1998
Předmět:
Male
Pituitary gland
Pro-Opiomelanocortin
medicine.medical_treatment
Gene Expression
Suppressor of Cytokine Signaling Proteins
Leukemia Inhibitory Factor
Mice
Endocrinology
Gene expression
Cytokine Receptor gp130
Phosphorylation
Lymphokines
Membrane Glycoproteins
biology
General Medicine
Transfection
Growth Inhibitors
Recombinant Proteins
DNA-Binding Proteins
medicine.anatomical_structure
Cytokine
Pituitary Gland
hormones
hormone substitutes
and hormone antagonists
STAT3 Transcription Factor
endocrine system
medicine.medical_specialty
Hypothalamus
Cell Line
Adrenocorticotropic Hormone
Proopiomelanocortin
Antigens
CD
Internal medicine
medicine
Animals
RNA
Messenger
Molecular Biology
Interleukin-6
Proteins
Molecular biology
Mice
Inbred C57BL
Repressor Proteins
Suppressor of Cytokine Signaling 3 Protein
Cell culture
Trans-Activators
biology.protein
Corticotropic cell
Leukemia inhibitory factor
Interleukin-1
Transcription Factors
Zdroj: Molecular Endocrinology. 12:954-961
ISSN: 1944-9917
0888-8809
Popis: As pituitary leukemia-inhibitory factor (LIF) mediates neuroimmune signals to the hypothalamo-pituitary-adrenal axis, we tested the role of intracellular SOCS-3 in corticotroph function. SOCS-3, a cytokine-inducible protein of the suppressor of cytokine signaling (SOCS) family, is expressed in the murine pituitary in vivo. After i.p. injection of LIF (5.0 micrograms/mouse) or interleukin-1 beta (0.1 microgram/mouse) pituitary SOCS-3 mRNA was stimulated 9-fold and 6-fold, respectively. Also, in corticotroph AtT-20 cells LIF and interleukin-1 beta both potently stimulated SOCS-3 mRNA expression. In AtT-20 cells, stable overexpression of SOCS-3 inhibits basal and LIF-stimulated ACTH secretion in comparison to mock-transfected AtT-20 cells (basal: 4426 +/- 118 vs. 4973 +/- 138 pg/ml, P0.05; LIF-induced: 5511 +/- 172 vs. 9308 +/- 465 pg/ml, P0.001). Stable overexpression of SOCS-3 cDNA in AtT-20 cells also resulted in a significant 50% decrease of LIF-induced POMC mRNA levels (P0.05) and POMC promoter activity (P0.001), respectively. Western blot analysis revealed an inhibition of LIF-stimulated gp130 and STAT-3 phosphorylation in SOCS-3 overexpressing AtT-20 cells. Thus, SOCS-3 inhibits the Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathway, which is known to mediate LIF-stimulated ACTH secretion and POMC gene expression. In conclusion, SOCS-3 functions as an intracellular regulator of POMC gene expression and ACTH secretion, acting as a negative feedback mediator of the cytokine-mediated neuro-immuno-endocrine interface.
Databáze: OpenAIRE
Externí odkaz: