Study on the regulation of CRF receptor

为探讨促肾上腺皮质激素（ACTH）分泌不足和库欣病的病理生理机制，研究了大鼠垂体前叶（AP）和人垂体促肾上腺皮质激素腺瘤细胞中促肾上腺皮质激素1型受体（CRF-R）基因和蛋白水平的差异。在体外培养的大鼠垂体前叶细胞中，CRF、cAMP、VP和地塞米松孵育1小时后，CRF-R mRNA水平下调。另一方面，在促肾上腺皮质激素腺瘤细胞中，这些水平被CRF和cAMP上调，而被VP和地塞米松下调。以大鼠CRF-R C-末端抗血清和CRF-R C-末端片段为示踪剂和标准品，用CRF-R RIA测定了大鼠AP体内和体外CRF-R蛋白水平的变化。结果表明，CRF-cAMP系统在mRNA和蛋白水平下调CRF-R，并参与了库欣病垂体微腺瘤向纳尔逊综合征大腺瘤的发展。CRF-cAMP系统、VP和地塞米松对CRF-R mRNA稳定性的影响有待进一步研究。

To clarify the pathophysiology of ACTH insufficiency and Cushing's disease, the difference of the regulatory mechanism of CRF type 1 receptor (CRF-R) gene and protein levels between rat anterior pituitary (AP) and human pituitary corticotroph adenoma cells were studied.AP CRF-R mRNA levels temporarily decreased 1-7 days after bilateral adrenalectomy, and these levels returned to the control level 14 days after surgery. In the rat anterior pituitary cells in vitro, CRF-R mRNA levels were down-regulated 1 hr after incubation with CRF,cAMP,VP and dexamethasone. On the other hand, these levels were up-regulated by CRF and cAMP,but were down-regulated by VP and dexamethasone in corticotroph adenoma cells. Changes in CRF-R protein levels in rat AP in vivo and in vitro were also determined by CRF-R RIA using rat CRF-R C-terminal antiserum and CRF-R C-terminal fragment as a tracer and a standard. CRF-R protein levels also decreased after adrenalectomy and incubation with CRF and cAMP.These results indicate that the CRF-cAMP system down-regulates CRF-R at mRNA and protein levels and also suggest that the CRF-cAMP system is involved in the mechanism of the development of pituitary microadenoma of Cushing's disease to macroadenoma of Nelson syndrome. Effects of the CRF-cAMP system, VP and dexamethasone on the stability of CRF-R mRNA should be clarified in the near future.