The Regulatory Effect And Related Mechanism Of High Dose Of Glucocorticoid On The Synthesis Of Corticotrophin-releasing Hormone In PVN

Corticotrophin-releasing hormone (CRH) is known as the primary hormone in hypothalamus-pituitary-adrenal axis (HPA axis) to trigger the responding of HPA axis to stressor; and CRH also involves in the activation of sympathetic-adrenal medulla system. In this way, CRH is recognized as one of the most important promoters in stress response and can be regarded as the objective index to reflect the stress status.Traditionally, glucocorticoid (GC) binding to intracellular glucocorticoid receptor (iGR) can directly and/or indirectly suppress the expression of CRH. So, high dose of GC should have strongly negative-feedback inhibition to CRH.However, some researches showed that high dose of GC (≥10-6mol/L) hadn't totally down-regulated the CRH synthesis in PVN, which indicated there may be more complex modulation mechanism of GC in the course of CRH synthesis and secretion. In addition, the serum concentration of high dosage is 1000 times greater than the physiological concentration, and that is far beyond the required amount to saturate iGR as well. These all hint the contradictive phenomena to iGR may correlate to newly noted membrane glucocorticoid receptor (mGR) closely. Hence, we postulate that high dose of GC would regulate the CRH synthesis and secretion via mGR.Objective:(1) to elaborate the effect of high dose of GC on the CRH gene transcription and protein expression; (2) to grope for the reasonable mechanisms and pathways different with iGR of high dose of GC to CRH transcription and expression. By this researching, the mechanism related to CRH persistent increase, to the therapeutic function of high dose of GC can be discussed, which may furnish some new ideas to the clinic applications of high dose of GC at the early stage of severe trauma.Method:1. The changes in CRH protein and mRNA expression under different GC conditions...