Regulation of corticotropin releasing hormone receptor type 1 messenger RNA level in Y-79 retinoblastoma cells: potential implications for human stress response and immune/inflammatory reaction

N C Vamvakopoulos,P C Avgerinos,T O Sioutopoulou,P Marcoulatos,Z Mamuris

doi:10.1155/s0962935196000476

Abstract

We report the regulation of type 1 receptor mRNA in Y-79 human retinoblastoma cells, grown in the absence or presence of pharmacological levels of phorbol esters, forskolin, glucocorticoids and their combinations. To control for inducibility and for assessing the sensitivity of the Y-79 system to glucocorticoids, corticotropin releasing hormone mRNA levels were measured in parallel. All treatments stimulated corticotropin releasing hormone receptor type 1 gene expression relative to baseline. A weak suppression of corticotropin releasing hormone mRNA level was observed during dexamethasone treatment. The cell line expressed ten-fold excess of receptor to ligand mRNA under basal conditions. The findings predict the presence of functional phorbol ester, cyclic AMP and glucocorticoid response elements in the promoter region of corticotropin releasing hormone receptor type 1 gene and support a potential role for its product during chronic stress and immune/inflammatory reaction.

Highlights

Stress response is a major survival resource and an important permissive factor of primal life properties such as growth, reproduction, evolution and adaptation
We report the effect of forskolin, phorbol esters, dexamethasone and their combinations, on corticotropin releasing hormone receptor (CRHR) type 1 mRNA levels in Y-79 cells, using corticotropin releasing hormone (CRH) mRNA coexpression as induction control
We studied the regulation of CRHR type 1 mRNA in Y-79 human retinoblastoma cells by phorbol esters, forskolin, glucocorticoids and their combinations, using CRH gene coexpression as internal control

Summary

Introduction

Stress response (the organism’s ability for adaptive homeostasis) is a major survival resource and an important permissive factor of primal life properties such as growth, reproduction, evolution and adaptation. In mammals, unexpected stimulation or stress, activates the heat shock protein (hsp) system at the cellular level, and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. :328 Mediators of Inflammation Vol 5 1996 in the brain,[12] and type 213-15 with its two splice variant isoforms; z expressed in limited areas of the brain[14] and [3 expressed in peripheral tissues including the duodenum, skeletal muscle, epididymis and perivascular cells of the heart,1316 and the binding protein (CRHBP), 7 is central coordinator of HPA axis activity and acts in concert with glucocorticoids to maintain whole body homeostasis. Animal studies revealed highly complex regulation and tissue-specific expression patterns of CRH system components, using a variety of molecular probes.5’12.’16 18 21 To this end, studies with cell lines expressing components of the CRH system, either naturally or following transfection, provide valuable alternatives to the multiparametric complexity inherent in the animal model systems approach and complement molecular analyses of critical regulatory aspects.[22,23,24,25]

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