摘要
本课题组的研究发现,抑郁症病人下丘脑室旁核促肾上腺皮质激素释放激素(CRH)神经元上雌激素和雄激素受体表达增加,性激素与CRH神经元上的性激素受体结合,作用于CRH启动子上的性激素反应单元调节CRH的转录活性,雌激素可增加CRH的表达而雄激素可抑制CRH的活性.除性激素受体外,抑郁症病人下丘脑内调控CRH神经元活性的许多其他受体也表现为平衡紊乱.靶向于糖皮质激素和性激素受体的药物可能通过作用于海马不同区域的神经元,调控抑郁症动物的相关行为.根据上述发现,我们提出抑郁症发病的多受体平衡紊乱假说.
Our recent studies reported that the expression of estrogen receptor （ER） and androgen receptor （AR） in corticotropin-releasing hormone （CRH） neurons in the paraventricular nucleus （PVN） of hypothalamus increases in depressed patients. Estrogen and androgen can modulate the transcription activity of CRH by binding ER or AR, which act on the estrogen response elements （EREs） and androgen response elements （AREs） on the human CRH gene promoter respectively. Androgen inhibits the activity of the CRH gene promoter while estrogen activates CRH gene expression. In addition to ER and AR, multiple receptors in the hypothalamus which regulate the activity of CRH neurons show a disturbed balance in depressed patients. Drug targeting to glucocorticoid receptors and sex hormone receptors might be useful for improving depressive behavior by modulating the neurons of different areas in the hippocampus. Based on these findings, we proposed the hypothesis that imbalances of multiple receptors in the hypothalamus may contribute to depression.
基金
国家自然科学基金重点项目(30530310)资助
