The translational aspects of glucocorticoid biorhythmicity in modern therapeutics

Konstantinos Kalafatakis
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Abstract

Glucocorticoids are a class of steroid hormones, vital for mammalian life. They have a plethora of biological effects, mainly supporting metabolic, cognitive, and immunological functions. The pharmacological use of glucocorticoids makes them one of the most frequently prescribed drugs across all continents, and in all types of forms. Nevertheless, a number of serious adverse effects accompany the prolonged treatment with high doses of glucocorticoids. Research developments over the last 20 years have gradually reshaped the way we think about glucocorticoid-based therapeu¬tics. Aside their circadian rhythm and their delayed regulatory influence over an extensive number of sensitive genes, glucocorticoids also possess an underlying, ultradian rhythm, and also exert rapid, non-genomic effects. The notion that chronicity of glucocorticoid stimulation may differentially modulate the type of biological effects of the hormone brings various chronopharmacological concepts on the table of modern glucocorticoid-based therapeutics.
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糖皮质激素生物节律在现代疗法中的转化问题
糖皮质激素是一类类固醇激素,对哺乳动物的生命至关重要。它们具有多种生物效应,主要支持代谢、认知和免疫功能。糖皮质激素的药理作用使其成为各大洲最常用的处方药之一,而且形式多样。然而,长期使用大剂量糖皮质激素会产生一些严重的不良反应。过去 20 年的研究进展逐渐改变了我们对糖皮质激素治疗的看法。除了昼夜节律和对大量敏感基因的延迟调控影响外,糖皮质激素还具有潜在的超昼夜节律,并能迅速产生非基因组效应。糖皮质激素的长期刺激可能会对激素的生物效应类型产生不同的调节作用,这一观点为现代糖皮质激素疗法带来了各种时药学概念。
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