Upregulation of interleukin-1 receptors in mouse AtT-20 pituitary tumor cells following treatment with corticotropin-releasing factor.
Treatment of AtT-20 cell cultures with increasing concentrations of rat/human corticotropin-releasing factor (r/hCRF) for 24 h resulted in a dose-dependent 2-3 fold increase in specific 125I-labelled recombinant human IL-1 alpha (125I-IL-1 alpha) binding that was paralleled by a 70-80% decrease in 125I-Tyro-ovine CRF binding. Saturation analysis of 125I-IL-1 alpha binding in control and CRF-treated cultures indicated that CRF produced an increase in the density (Bmax) of IL-1 receptors without altering their affinity (KD). The CRF-induced upregulation of IL-1 receptors appears to be mediated through specific membrane receptors for CRF since the CRF receptor antagonist, alpha-helical oCRF (9-41), blocked the CRF-induced upregulation of IL-1 receptors without producing any effect on 125I-IL-1 alpha binding by itself. In summary, these data demonstrate complex interactions between CRF and IL-1 at the pituitary level and identify potential novel mechanisms for cytokines to alter neuroendocrine function.
Webster
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EL
Neurobiology Laboratory, National Institute on Drug Abuse, Baltimore, MD 21224.
Tracey
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De Souza
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EB
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D003346:Corticotropin-Releasing Hormone