Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Int J Mol Sci. 2024 Oct 3;25(19):10658. doi: 10.3390/ijms251910658.
Vertebrates exhibit a left-right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in the neuroendocrine system, responsible for producing steroid hormones under stimuli. In the present study, the lateralized asymmetry of left and right adrenal glands in leptin receptor-deficit db/db mice was investigated. First, a morphological and histological examination showed that adrenal mass and adrenal cortex volume in db/db mice were significantly higher than in non-diabetic control mice. Then, adrenal transcriptomic and serum metabolomic analyses were performed. Adrenal steroid profiling showed that the levels of corticosterone and aldosterone in the right adrenal gland of db/db mice were two times higher than in the left one. The expression of multiple genes related to adrenal regeneration and innervation in db/db mice was reduced in contrast to the increased steroid hormone secretion. Furthermore, an examination of morphogens in asymmetric adrenal development revealed a significant differential expression of Shh and its receptor gene Ptch1. In conclusion, the present study has provided evidence that a superior steroidogenesis exists in the right adrenal gland of db/db mice and suggested that Shh signaling may play an important role in asymmetric adrenal responses in type 2 diabetes and its complications.
脊椎动物从中枢结构到周围成对的内分泌器官都表现出左右不对称。然而，配对内分泌腺的不对称性及其不对称性的病理后果在很大程度上仍然未知。肾上腺是神经内分泌系统中的一对周围终末器官，负责在刺激下产生类固醇激素。在本研究中，研究了瘦素受体缺陷 db/db 小鼠左右肾上腺的偏侧不对称性。首先，形态学和组织学检查表明，db/db 小鼠的肾上腺质量和肾上腺皮质体积明显高于非糖尿病对照小鼠。然后进行了肾上腺转录组和血清代谢组分析。肾上腺类固醇谱分析显示，db/db 小鼠右侧肾上腺的皮质酮和醛固酮水平是左侧的两倍。与类固醇激素分泌增加相反，与肾上腺再生和神经支配有关的多个基因的表达减少。此外，对不对称肾上腺发育中形态发生素的检查显示 Shh 及其受体基因 Ptch1 的表达存在显著差异。总之，本研究提供了证据表明 db/db 小鼠右侧肾上腺存在更高的类固醇生成能力，并表明 Shh 信号可能在 2 型糖尿病及其并发症的不对称肾上腺反应中发挥重要作用。
