Cytokine-Mediated Growth Hormone Release from Cultured Ovine Pituitary Cells

Autor: James L. Sartin, Barbara P Steele, Christa L. Fry, David R. Gunter, Christopher D. McMahon
Rok vydání: 1998
Předmět:
Male
medicine.medical_specialty
Nifedipine
Lipopolysaccharide
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Radioimmunoassay
Cyclic AMP-Dependent Protein Kinase Type II
Biology
Growth hormone
Gonadotropin-Releasing Hormone
Interferon-gamma
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Endocrinology
Pituitary Gland
Anterior
Interferon
Internal medicine
Pi
medicine
Animals
Masoprocol
Protein kinase A
Cells
Cultured
Sheep
Tumor Necrosis Factor-alpha
Endocrine and Autonomic Systems
Interleukin
Calcium Channel Blockers
5
8
11
14-Eicosatetraynoic Acid
Cyclic AMP-Dependent Protein Kinases
Cytokine
chemistry
Growth Hormone
Cytokines
Interleukin-2
Tetradecanoylphorbol Acetate
Tumor necrosis factor alpha
Somatostatin
Orchiectomy
Interleukin-1
Signal Transduction
medicine.drug
Zdroj: Neuroendocrinology. 68:192-200
ISSN: 1423-0194
0028-3835
DOI: 10.1159/000054366
Popis: Previous studies have demonstrated that intravenous lipopolysaccharide (LPS) will increase concentrations of growth hormone (GH). One possible explanation for this may reside in the response of the pituitary to specific cytokines. This study sought to determine the effects of recombinant bovine tumor necrosis factor α (TNF), recombinant ovine (ro) interleukin-1α (IL-1α), roIL-1β, ro interleukin-2 (IL-2), and ro γ-interferon (INT) on GH release from cultured sheep pituitary cells. Sheep were sacrificed and pituitary cells cultured in DMEM with 10% fetal bovine serum for 3 days. On day 4, cells were washed and serum-free DMEM added to cells. IL-1α and IL-1β were used at 0.2, 2 and 20 ng/ml and the remaining cytokines at 2, 20 and 200 ng/ml. Neither IL-2 nor INT had effects on basal or on GH-releasing hormone (GRH)-stimulated GH release. TNF inhibited GRH-stimulated GH release (p < 0.05). Both IL-1α and IL-1β stimulated GH release from cultured pituitary cells at all doses tested (p < 0.01). Neither IL-1α nor IL-1β had an effect on GRH-stimulated GH release. IL-1 effects were inhibited by H-89 (p < 0.05; a protein kinase A inhibitor) and by nifedipine (p < 0.05; a calcium channel blocker). Both of these mechanisms are central signal transduction mechanisms mediating GRH-stimulated GH release. IL-1-stimulated GH release is partially inhibited (p < 0.05) by lipoxygenase pathway blockers. Phorbol myristate acetate downregulation of protein kinase C did not alter IL-1-stimulated GH release. IL-1β increased the content of both GH and GH mRNA in cultured sheep pituitary cells. We conclude that IL-1 produces a strong stimulus to GH release, which is mediated by calcium entry and protein kinase A activation. IL-1 also activates lipoxygenase pathways. This latter pathway as well as calcium entry were shown to mediate LPS stimulation of GH release from cultured pituitary cells. The similarity between IL-1 and LPS signal transduction suggests that LPS may activate pituitary production of IL-1 to produce the stimulus to GH. The lack of inhibitory effects of INT, TNF and IL-2 as opposed to what is seen in the rat may suggest a partial mechanism to explain the different effects of LPS on GH release between sheep and that seen in cattle and rats.
Databáze: OpenAIRE
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