PTC Therapeutics, Inc, South Plainfield, NJ, USA.
1434Texas Commission on Environmental Quality, Austin, TX, USA.
Toxicol Pathol. 2021 Jul;49(5):1117-1125. doi: 10.1177/01926233211009492. Epub 2021 Jun 2.
The most common target organ for toxicity in the endocrine system is the adrenal gland, and its function is dependent upon the hypothalamus and pituitary gland. Histopathologic examination of the adrenal glands and pituitary gland is routinely performed in toxicity studies. However, the function of the adrenal gland is not routinely assessed in toxicity studies. Assessment of adrenal cortical function may be necessary to determine whether a histopathologic finding in the adrenal cortex results in a functional effect in the test species. As juvenile toxicity studies are more commonly performed in support of pediatric indications for pharmaceuticals, it is important to establish historical control data for adrenal gland function. In this study, adrenal cortical function was assessed in control neonatal and weanling beagle dogs as part of an ongoing juvenile toxicology program. Measurements of serum adrenocorticotropic hormone (ACTH), cortisol prior to and following administration of exogenous ACTH, and aldosterone were conducted beginning at 2 weeks of age continuing through 26 weeks of age. Serum electrolyte concentrations were determined at 4, 13, and 26 weeks of age. Dogs as young as 2 weeks of age synthesize and secrete adrenal cortical hormones and exhibit a functional hypothalamic pituitary adrenal axis.
内分泌系统中毒的最常见靶器官是肾上腺，其功能依赖于下丘脑和垂体。毒理学研究中通常对肾上腺和垂体进行组织病理学检查。然而，毒理学研究中通常不评估肾上腺的功能。评估肾上腺皮质功能可能对于确定肾上腺皮质的组织病理学发现是否导致测试物种的功能效应是必要的。由于儿科药物的支持下更常进行幼年毒性研究，因此建立肾上腺功能的历史对照数据非常重要。在这项研究中，作为正在进行的幼年毒理学计划的一部分，评估了对照新生和断奶比格犬的肾上腺皮质功能。在 2 周龄时开始进行血清促肾上腺皮质激素（ACTH）、外源性 ACTH 给药前后皮质醇以及醛固酮的测量，并持续到 26 周龄。在 4、13 和 26 周龄时测定血清电解质浓度。2 周龄的幼犬即可合成和分泌肾上腺皮质激素，并表现出功能性下丘脑-垂体-肾上腺轴。
