Health Care Center, Kochi University, Kochi city, Kochi 780-8520, Japan.
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku city, Kochi 783-8505, Japan.
Endocrinology. 2022 Oct 23;163(12). doi: 10.1210/endocr/bqac173.
Endogenous Cushing's syndrome is characterized by unique clinical features and comorbidities, and progress in the analysis of its genetic pathogenesis has been achieved. Moreover, prescribed glucocorticoids are also associated with exogenous Cushing's syndrome. Several animal models have been established to explore the pathophysiology and develop treatments for Cushing's syndrome. Here, we review recent studies reporting animal models of Cushing's syndrome with different features and complications induced by glucocorticoid excess. Exogenous corticosterone (CORT) administration in drinking water is widely utilized, and we found that CORT pellet implantation in mice successfully leads to a Cushing's phenotype. Corticotropin-releasing hormone overexpression mice and adrenal-specific Prkar1a-deficient mice have been developed, and AtT20 transplantation methods have been designed to examine the medical treatments for adrenocorticotropic hormone-producing pituitary neuroendocrine tumors. We also review recent advances in the molecular pathogenesis of glucocorticoid-induced complications using animal models.
内源性库欣综合征的特点是具有独特的临床特征和合并症,其遗传发病机制的分析也取得了进展。此外,皮质激素的处方也与外源性库欣综合征有关。已经建立了几种动物模型来探索库欣综合征的病理生理学,并开发其治疗方法。在这里,我们回顾了最近的研究报告,这些研究报告了不同特征和由皮质醇过多引起的并发症的库欣综合征动物模型。在饮用水中给予外源性皮质酮(CORT)的方法被广泛应用,我们发现 CORT 微囊植入小鼠可成功导致库欣表型。已经开发了促肾上腺皮质激素释放激素过表达小鼠和肾上腺特异性 Prkar1a 缺陷小鼠,并设计了 AtT20 移植方法来检查促肾上腺皮质激素产生的垂体神经内分泌肿瘤的治疗方法。我们还回顾了使用动物模型研究皮质激素诱导的并发症的分子发病机制的最新进展。