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精神分裂症男性的类固醇组学。

Steroidomics in Men with Schizophrenia.

机构信息

Department of Steroids and Proteofactors, Institute of Endocrinology, Narodni 139/8, 110 00 Prague, Czech Republic.

Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia.

出版信息

Int J Mol Sci. 2024 Aug 10;25(16):8729. doi: 10.3390/ijms25168729.

DOI:10.3390/ijms25168729
PMID:39201417
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11354902/
Abstract

Schizophrenia is associated with numerous abnormalities, including imbalances in all hormonal axes, among which steroids play a major role. Steroidomic studies therefore represent a promising tool for early diagnosis and appropriate treatment of schizophrenia. A total of 51 adult male schizophrenics aged 27 (22, 34) years (shown as median with quartiles) and 16 healthy controls (HCs) aged 28 (25, 32) years were enrolled into this study. Our results showed the effective differentiation of men with schizophrenia from controls based on steroidomic profiles. We also found an altered metabolic pathway from pregnenolone and its sulfate (PREG/S) to cortisol in schizophrenics with several metabolic bottlenecks such as lower PREG levels due to increased PREG sulfation and/or suppressed PREGS desulfation and attenuated conversion of 17-hydroxy-PREG to 17-hydroxy-progesterone, as well as the results suggestive of suppressed CYP11B1 activity. In contrast, steroid molar ratios suggested two counterregulatory steps involving increased conversion of PREG/S to 17-hydroxy-PREG/S and decreased conversion of cortisol to cortisone, which may maintain unchanged basal cortisol levels but may not ensure a sufficient cortisol response to stress. Our data also indicated a trend to higher 7α-, 7β-, and 16α-hydroxylation that may counteract the autoimmune complications and proinflammatory processes accompanying schizophrenia. Finally, a possible suppression of HSD17B3 activity was suggested, resulting in decreased circulating testosterone levels with increased androstenedione levels.

摘要

精神分裂症与许多异常有关，包括所有激素轴的失衡，其中类固醇起着主要作用。因此，类固醇组学研究代表了一种用于精神分裂症早期诊断和适当治疗的有前途的工具。本研究共纳入 51 名年龄为 27（22，34）岁的成年男性精神分裂症患者（中位数加四分位数）和 16 名年龄为 28（25，32）岁的健康对照者（HCs）。我们的结果表明，基于类固醇组学谱，可以有效区分男性精神分裂症患者和对照组。我们还发现，精神分裂症患者的孕烯醇酮及其硫酸盐（PREG/S）到皮质醇的代谢途径发生改变，存在几个代谢瓶颈，例如由于 PREG 硫酸化增加和/或 PREGS 去硫酸化抑制以及 17-羟基-PREG 向 17-羟基孕酮的转化减弱，导致 PREG 水平降低，以及 CYP11B1 活性受到抑制的结果。相比之下，类固醇摩尔比表明涉及增加 PREG/S 向 17-羟基-PREG/S 转化和减少皮质醇向可的松转化的两个反向调节步骤，这可能维持基础皮质醇水平不变，但不能确保皮质醇对压力有足够的反应。我们的数据还表明存在更高的 7α-、7β-和 16α-羟化趋势，这可能对抗伴随精神分裂症的自身免疫并发症和促炎过程。最后，可能存在 HSD17B3 活性的抑制，导致循环睾酮水平降低，雄烯二酮水平升高。

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