Dhillon G S, Oleshansky M A, Kant G J
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Cell Signal. 1989;1(3):295-301. doi: 10.1016/0898-6568(89)90047-8.
Corticotropin releasing hormone (CRH) stimulation of ACTH release and cyclic AMP-mediated events involved in the control of ACTH release were compared in sham-operated and adrenalectomized rats. CRH-stimulated adenylate cyclase activity was decreased in pituitary homogenates from adrenalectomized animals. CRH-stimulated cyclic AMP accumulation was essentially abolished and CRH-stimulated cyclic AMP-dependent protein kinase (A-kinase) activity was decreased in freshly prepared anterior pituitary cells from adrenalectomized animals. Basal and CRH-stimulated ACTH release was elevated in these cells. Since ACTH release is increased in adrenalectomized rats despite the down regulation of CRH-linked pituitary mechanisms, we speculate that the site of action of disinhibition by corticosterone of ACTH release (or synthesis) following adrenalectomy is distal to the generation of cyclic AMP and/or that non-CRH mediated mechanisms assume a greater role in ACTH regulation following adrenalectomy.
在假手术组和肾上腺切除大鼠中,比较了促肾上腺皮质激素释放激素(CRH)对促肾上腺皮质激素(ACTH)释放的刺激作用以及参与ACTH释放调控的环磷酸腺苷(cAMP)介导的事件。肾上腺切除动物的垂体匀浆中,CRH刺激的腺苷酸环化酶活性降低。在肾上腺切除动物新鲜制备的垂体前叶细胞中,CRH刺激的cAMP积累基本被消除,且CRH刺激的cAMP依赖性蛋白激酶(A激酶)活性降低。这些细胞中基础ACTH释放和CRH刺激的ACTH释放均升高。由于肾上腺切除大鼠中ACTH释放增加,尽管与CRH相关的垂体机制下调,我们推测肾上腺切除后皮质酮对ACTH释放(或合成)去抑制作用的作用位点在cAMP产生的远端,和/或非CRH介导的机制在肾上腺切除后的ACTH调节中发挥更大作用。