First Department of Pediatrics, Division of Endocrinology, Metabolism and Diabetes, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece.
Center of Clinical, Experimental Surgery and Translational Research, Division of Endocrinology and Metabolism, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
Int J Mol Sci. 2021 Oct 7;22(19):10839. doi: 10.3390/ijms221910839.
Glucocorticoids are the final products of the neuroendocrine hypothalamic-pituitary-adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management.
糖皮质激素是神经内分泌下丘脑-垂体-肾上腺轴的终产物，在受到威胁或被认为受到威胁时，通过重新建立体内平衡来发挥重要的应激反应作用。这些甾体激素通过与其同源受体——人类糖皮质激素受体结合发挥多种作用，后者作为配体结合转录因子，诱导或抑制大量靶基因的表达。为了实现体内平衡，糖皮质激素信号应该对所有组织都有最佳的效果。事实上，任何数量或质量上不适当的糖皮质激素作用都与病理状况有关，这些状况的特点是短期或长期的有害影响。本文讨论了两种这样的情况，即原发性全身性糖皮质激素抵抗和超敏综合征。毫无疑问，结构、分子和细胞生物学的巨大进步，以及生物技术的持续进步，导致了对这些罕见内分泌疾病的更好、更深入的理解，以及更有效的治疗管理。
