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Vitamin D and evolution: Pharmacologic implications

机译：维生素D和进化：药理学意蕴

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Vitamin D-3 is produced non-enzymatically when the cholesterol precursor 7-dehydrocholesterol is exposed to UV-B, i.e., evolutionary the first function of the molecule was that of an UV-B radiation scavenging end product. Vitamin D endocrinology started when some 550 million years ago first species developed a vitamin D receptor (VDR) that binds with high affinity the vitamin D metabolite 1 alpha,25-dihydroxyvitamin D-3. VDR evolved from a subfamily of nuclear receptors sensing the levels of cholesterol derivatives, such as bile acids, and controlling metabolic genes supporting cellular processes, such as innate and adaptive immunity. During vertebrate evolution, the skeletal and adaptive immune system showed in part interesting synchronous development although adaptive immunity is evolutionary older. There are bidirectional osteoimmune interactions between the immune system and bone metabolism, the regulation of both is under control of vitamin D. This diversity of physiological functions explains the pleiotropy of vitamin D signaling and opens the potential for various pharmacological applications of vitamin D as well as of its natural and synthetic derivatives. The overall impact of vitamin D on human health is demonstrated by the fact that the need for its efficient synthesis served in European hunter and gatherers as an evolutionary driver for increased 7-dehydrocholesterol levels, while light skin was established far later via populations from Anatolia and the northern Caucasus entering Europe 9000 and 5000 years ago, respectively. The later population settled preferentially in northern Europe and we hypothesize that that the introduction of high vitamin D responsiveness was an essential trait for surviving dark winters without suffering from the detrimental consequences of vitamin D deficiency.
机译：当胆固醇前体7-脱羟基氯甾醇暴露于UV-B时，维生素D-3是非酶促生产的，即，进化分子的第一功能是UV-B辐射清除最终产品的第一功能。维生素D内分泌始于约5.5亿年前的第一个物种开发了一种维生素D受体（VDR），其与高亲和力的维生素D代谢物1α，25-二羟基维生素D-3结合。 VDR从核受体的亚家族中演变，感测胆固醇衍生物等水平，例如胆汁酸，并控制支持细胞过程的代谢基因，例如先天和适应性免疫。在脊椎动物进化中，骨骼和自适应免疫系统部分表现出有趣的同步发展，尽管适应性豁免是进化较大的。免疫系统和骨代谢之间的双向骨瘤相互作用，两者的调节都受到维生素D的控制。这种生理功能的多样性解释了维生素D信号传导的亲生物，并打开了维生素D的各种药理学应用的可能性其天然和合成衍生物。维生素D对人类健康的总体影响是通过在欧洲猎人和收集者中服务的有效合成作为进化驱动器的需求增加了7-脱羟基醇水平的进化驱动器，而轻微的皮肤在植物中的群体以后的群体成立。北高加索分别进入欧洲9000和5000年前。后来的人口优先在北欧定居，我们假设介绍高维生素D响应性的引入是幸存的黑暗冬季的重要特征，而不会患维生素D缺乏的不利后果。

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