Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice.

摘要: Corticotropin-releasing hormone (CRH) is both a main regulator of the hypothalamic-pituitary-adrenocortical axis and autonomic nervous system. CRH receptor type 1 (CRHR1)-deficient mice demonstrate alterations in behavior, impaired stress responses with adrenocortical insufficiency aberrant neuroendocrine development, but adrenal medulla has not been analyzed these animals. Therefore we studied production catecholamines, expression enzyme responsible for catecholamine biosynthesis neuropeptides ultrastructure chromaffin cells CRHR1 null mice. In addition examined whether treatment adrenocorticotropic (ACTH) could restore function medulla. received saline or ACTH, wild-type heterozygous injected served as controls. Adrenal epinephrine levels saline-treated were 44% those controls (P<0.001), phenylethanolamine N-methyltransferase (PNMT) mRNA only 25% (P <0.001). ACTH increased PNMT level failed to them normal levels. Proenkephalin saline- ACTH-treated higher than control animals (215.8% P <0.05, 268.9% <0.01) whereas neuropeptide Y chromogranin B did differ. On ultrastructural level, exhibited marked depletion epinephrine-storing secretory granules that was completely normalized by ACTH-treatment. conclusion, required cell structure deletion this gene associated significant impairment biosynthesis.