Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Pre-analytical stability and physiological fluctuations affect plasma steroid hormone outcomes: A real-world study","authors":"Jian Zhong ,&nbsp;Danchen Wang ,&nbsp;Shaowei Xie ,&nbsp;Ming Li ,&nbsp;Yicong Yin ,&nbsp;Jialei Yu ,&nbsp;Chaochao Ma ,&nbsp;SongLin Yu ,&nbsp;Ling Qiu","doi":"10.1016/j.jsbmb.2024.106596","DOIUrl":"10.1016/j.jsbmb.2024.106596","url":null,"abstract":"<div><p>Since steroids are crucial for diagnosing endocrine disorders, the lack of research on factors that affect hormone levels makes interpreting the results difficult. Our study aims to assess the stability of the pre-analytical procedure and the impact of hormonal physiological fluctuations using real-world data. The datasets were created using 12,418 records from individuals whose steroid hormone measurements were taken in our laboratory between September 2019 and March 2024. 22 steroid hormones in plasma by a well-validated liquid chromatography tandem mass spectrometry method were measured. After normalization transformation, outlier removal, and z-score normalization, generalized additive models were constructed to evaluate preanalytic stability and age, sex, and sample time-dependent hormonal fluctuations. Most hormones exhibit significant variability with age, particularly steroid hormone precursors, sex hormones, and certain corticosteroids such as aldosterone. 18-hydroxycortisol, 18-oxocortisol. Sex hormones varied between males and females. Levels of certain hormones, including cortisol, cortisone, 11-deoxycortisol, 18-hydroxycortisol, 18-oxocortisol, corticosterone, aldosterone, estrone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, 11-ketotestosterone, and 11-hydroxytestosterone, fluctuated with sampling time. Moreover, levels of pregnenolone and progesterone decreased within 1 hour of sampling, with pregnenolone becoming unstable with storage time at 4 degrees after centrifugation, while other hormone levels remained relatively stable for a short period of time without or after centrifugation of the sample. This is the first instance real-world data has been used to assess the pre-analytic stability of plasma hormones and to evaluate the impact of physiological factors on steroid hormones.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of aldosterone biosynthesis during fetal and pediatric periods; Histological analysis of CYP11B2-positive cell distribution in the zona glomerulosa of human adrenal","authors":"Tsubasa Shironomae ,&nbsp;Yuto Yamazaki ,&nbsp;Junji Takeyama ,&nbsp;Kiyohide Sakai ,&nbsp;Hironobu Sasano ,&nbsp;Takashi Suzuki","doi":"10.1016/j.jsbmb.2024.106593","DOIUrl":"10.1016/j.jsbmb.2024.106593","url":null,"abstract":"<div><p>The distribution of CYP11B2-positive or aldosterone producing adrenocortical cells in human fetuses and children and their age-dependent changes has not been studied. We aimed to explore the changes of aldosterone biosynthesis and age-related histological alterations of the zona glomerulosa in human adrenal gland during fetal and pediatric periods. We first reviewed 125 fetal and pediatric autopsy cases and retrieved 78 adrenals from 70 cases. CYP11B2 immunohistochemistry and quantitative image analysis of its results were performed in all adrenal glands. The ratio of the definitive zone (DZ) or zona glomerulosa (ZG) / the whole adrenocortical areas started to increase in the 2nd trimester, subsequently decreased in the 3rd, increased after birth, peaked in infancy, and then gradually decreased. The ratio of CYP11B2-positive / whole adrenocortical areas remained low during the fetal period but increased after birth, peaked at infancy, and then decreased. The ratio of CYP11B2-positive / DZ or ZG areas and CYP11B2-positive areas / depth of DZ or ZG demonstrated a distinctive bimodal pattern, with one peak in the fetal period and another in the neonatal period to infancy. This is the first study to perform quantitative analysis of the distribution of CYP11B2-positive cells, the histological DZ or ZG, and the development of aldosterone biosynthesis in human adrenal glands during fetal and pediatric periods.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0960076024001419/pdfft?md5=899c91d409197a539bb97cef85722e12&pid=1-s2.0-S0960076024001419-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen receptor knockdown suggests its role in gonadal development regulation in Manila clam Ruditapes philippinarum","authors":"Min Ding ,&nbsp;Lianxue Han ,&nbsp;Jingjing Miao ,&nbsp;Xuening Wang ,&nbsp;Lu Wang ,&nbsp;Luqing Pan","doi":"10.1016/j.jsbmb.2024.106594","DOIUrl":"10.1016/j.jsbmb.2024.106594","url":null,"abstract":"<div><p>The estrogen receptor (ER), a ligand-dependent transcription factor, is critical for vertebrate reproduction. However, its role in bivalves is not well understood, with ongoing debates regarding its function in regulating reproduction similarly to vertebrates. To investigate ER's function, we conducted a 21-day RNA interference experiment focusing on its role in gonadal development in bivalves. Histological analyses revealed that ER inhibition significantly suppressed ovarian development in females and, conversely, promoted gonadal development in males. Additionally, levels of 17β-estrogen (E2) were markedly reduced in the gonads of both sexes following ER suppression. Transcriptomic analysis from RNA-seq of testes and ovaries after ER interference showed changes in the expression of key genes such as Vtg, CYP17, 3β-HSD, and 17β-HSD. These genes are involved in the estrogen signaling pathway and steroid hormone biosynthesis. Furthermore, ER suppression significantly affected the expression of genes linked to gametogenesis and the reproductive cycle. Our findings highlight ER's crucial, yet complex and sex-specific roles in gonadal development in bivalves, emphasizing the need for further detailed studies.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mediating role of steroid hormones in the relationship between bisphenol A and its alternatives bisphenol S and F exposure and preeclampsia","authors":"Yudong Pu ,&nbsp;Yue Du ,&nbsp;Jie He ,&nbsp;Shuzhen He ,&nbsp;Ya Chen ,&nbsp;Aitong Cao ,&nbsp;Yuhui Dang","doi":"10.1016/j.jsbmb.2024.106591","DOIUrl":"10.1016/j.jsbmb.2024.106591","url":null,"abstract":"<div><p>Steroid hormone imbalance is believed to increase the odds of developing PE. Bisphenol A (BPA) and its substitutes (e.g., bisphenol S (BPS) and bisphenol F (BPF)) have estrogen-like effects, and its exposure may be related to the development of preeclampsia (PE). To explore the effects of bisphenol exposure on maternal serum steroid hormones and the potential mediating role of steroid hormones in the association between bisphenol exposure and developing PE, concentrations of bisphenols and steroid hormones in serum samples of 383 pregnant women were examined before delivery (including 160 PE cases and 223 control cases). Multivariable logistic and linear models were used to explore the associations of maternal serum bisphenols concentrations with both maternal steroid hormones and PE risk. Mediation modeling was employed to evaluate the mediating role of steroid hormones in the association between bisphenols and PE. Results showed that maternal serum BPS concentrations were positively associated with testosterone (T) concentrations. The mediation analyses suggested that approximately 10.17 % of the associations between BPS concentrations and the development of PE might be mediated by maternal T. In conclusion<strong>,</strong> maternal exposure to BPS during pregnancy is linked to higher maternal T concentrations, which might increase the odds of developing PE. T might mediate the association between BPS exposure and the development of PE.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on 20-hydroxyprogesterone: Chiral resolution, content determination and progesterone-like activity","authors":"Yuexuan Cheng ,&nbsp;Shujing Yan ,&nbsp;Liangyun Li ,&nbsp;Shijie Du ,&nbsp;Chunhong Zhong ,&nbsp;Xiaoli Gao ,&nbsp;Chunli Chen","doi":"10.1016/j.jsbmb.2024.106592","DOIUrl":"10.1016/j.jsbmb.2024.106592","url":null,"abstract":"<div><p>20-hydroxyprogesterone (20-DHP) is a natural metabolite of progesterone which occurs with two diastereoisomers: 20α-DHP and 20β-DHP. They have drawn attention for their progesterone-like activity since the middle of the 20th century. However, the literature from that era bears witness to a lack of consensus regarding their specific effects. Considered that their stereoisomerism differences, it is essential to investigate their biological activities in vivo separately. In this study, we presented a chemical synthesis technique that yielded highly pure samples of 20α-DHP and 20β-DHP, and performed simultaneous content analysis. Subsequently, we examined and contrasted the progesterone-like properties of 20α-DHP, 20β-DHP, and a 1:1 mixture of 20α-DHP and 20β-DHP. The Morphological observations of the endometrium were conducted via Haematoxylin–eosin staining. Serum hormone levels were measured using enzyme-linked immunosorbent assays. Furthermore, real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry were employed to analyse the relevant mRNA and protein expression, respectively. Our comparison revealed that 20α-DHP and P4 share identical progesterone-like actions, while 20β-DHP exhibits partial similarity. The progesterone activity varied when the two were combined in a 1:1 ratio.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Free fatty acids induce bile acids overproduction and oxidative damage of bovine hepatocytes via inhibiting FXR/SHP signaling","authors":"Zhiyuan Fang ,&nbsp;Zhiru Zhou ,&nbsp;Lingxue Ju ,&nbsp;Qi Shao ,&nbsp;Yongwei Xu ,&nbsp;Yuxiang Song ,&nbsp;Wenwen Gao ,&nbsp;Lin Lei ,&nbsp;Guowen Liu ,&nbsp;Xiliang Du ,&nbsp;Xinwei Li","doi":"10.1016/j.jsbmb.2024.106589","DOIUrl":"10.1016/j.jsbmb.2024.106589","url":null,"abstract":"<div><p>Hepatic oxidative injury induced by free fatty acids (FFA) and metabolic disorders of bile acids (BA) increase the risk of metabolic diseases in dairy cows during perinatal period. However, the effects of FFA on BA metabolism remained poorly understood. In present study, high concentrations of FFA caused cell impairment, oxidative stress and BA overproduction. FFA treatment increased the expression of BA synthesis-related genes [cholesterol 7a-hydroxylase (<em>CYP7A1</em>), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7, sterol 12α-hydroxylase, sterol 27-hydroxylase and oxysterol 7α-hydroxylase], whereas reduced BA exportation gene (ATP binding cassette subfamily C member 1) and inhibited farnesoid X receptor/small heterodimer partner (FXR/SHP) pathway in bovine hepatocytes. Knockdown of nuclear receptor subfamily 1 group H member 4 (<em>NR1H4</em>) worsened FFA-caused oxidative damage and BA production, whereas overexpression <em>NR1H4</em> ameliorated FFA-induced BA production and cell oxidative damage. Besides, reducing BA synthesis through knockdown of <em>CYP7A1</em> can alleviate oxidative stress and hepatocytes impairment caused by FFA. In summary, these data demonstrated that regulation of FXR/SHP-mediated BA metabolism may be a promising target in improving hepatic oxidative injury of dairy cows during high levels of FFA challenges.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroactive steroids fluctuate with regional specificity in the central and peripheral nervous system across the rat estrous cycle","authors":"Lucia Cioffi ,&nbsp;Silvia Diviccaro ,&nbsp;Gabriela Chrostek ,&nbsp;Donatella Caruso ,&nbsp;Luis Miguel Garcia-Segura ,&nbsp;Roberto Cosimo Melcangi ,&nbsp;Silvia Giatti","doi":"10.1016/j.jsbmb.2024.106590","DOIUrl":"10.1016/j.jsbmb.2024.106590","url":null,"abstract":"<div><p>Neuroactive steroids (i.e., sex steroid hormones and neurosteroids) are important physiological regulators of nervous function and potential neuroprotective agents for neurodegenerative and psychiatric disorders. Sex is an important component of such effects. However, even if fluctuations in sex steroid hormone level during the menstrual cycle are associated with neuropathological events in some women, the neuroactive steroid pattern in the brain across the ovarian cycle has been poorly explored. Therefore, we assessed the levels of pregnenolone, progesterone, and its metabolites (i.e., dihydroprogesterone, allopregnanolone and isoallopregnanolone), dehydroepiandrosterone, testosterone and its metabolites (i.e., dihydrotestosterone, 3α-diol and 17β-estradiol) across the rat ovarian cycle to determine whether their plasma fluctuations are similar to those occurring in the central (i.e., hippocampus and cerebral cortex) and peripheral (i.e., sciatic nerve) nervous system. Data obtained indicate that the plasma pattern of these molecules generally does not fully reflect the events occurring in the nervous system. In addition, for some neuroactive steroid levels, the pattern is not identical between the two brain regions and between the brain and peripheral nerves. Indeed, with the exception of progesterone, all other neuroactive steroids assessed here showed peculiar regional differences in their pattern of fluctuation in the nervous system during the estrous cycle. These observations may have important diagnostic and therapeutic consequences for neuropathological events influenced by the menstrual cycle.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0960076024001389/pdfft?md5=2ce57669eabff3bd93a849647c3312d6&pid=1-s2.0-S0960076024001389-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSA, an outdated biomarker for prostate cancer: In search of a more specific biomarker, citrate takes the spotlight","authors":"Lucas Galey ,&nbsp;Ayokunle Olanrewaju ,&nbsp;Hermann Nabi ,&nbsp;Jean-Sébastien Paquette ,&nbsp;Frédéric Pouliot ,&nbsp;Étienne Audet-Walsh","doi":"10.1016/j.jsbmb.2024.106588","DOIUrl":"10.1016/j.jsbmb.2024.106588","url":null,"abstract":"<div><p>The prevailing biomarker employed for prostate cancer (PCa) screening and diagnosis is the prostate-specific antigen (PSA). Despite excellent sensitivity, PSA lacks specificity, leading to false positives, unnecessary biopsies and overdiagnosis. Consequently, PSA is increasingly less used by clinicians, thus underscoring the imperative for the identification of new biomarkers. An emerging biomarker in this context is citrate, a molecule secreted by the normal prostate, which has been shown to be inversely correlated with PCa. Here, we discuss about PSA and its usage for PCa diagnosis, its lack of specificity, and the various conditions that can affect its levels. We then provide our vision about what we think would be a valuable addition to our PCa diagnosis toolkit, citrate. We describe the unique citrate metabolic program in the prostate and how this profile is reprogrammed during carcinogenesis. Finally, we summarize the evidence that supports the usage of citrate as a biomarker for PCa diagnosis, as it can be measured in various patient samples and be analyzed by several methods. The unique relationship between citrate and PCa, combined with the stability of citrate levels in other prostate-related conditions and the simplicity of its detection, further accentuates its potential as a biomarker.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary curcumin supplementation attenuates hepatic damage and function abnormality in a chronic corticosterone-induced stress model in broilers","authors":"Xuemei Shan ,&nbsp;Xingyu Xu ,&nbsp;Lijun Wang ,&nbsp;Yao Lu ,&nbsp;Xinyu Chen ,&nbsp;Fei Li ,&nbsp;Min Du ,&nbsp;Hua Xing ,&nbsp;Shifeng Pan","doi":"10.1016/j.jsbmb.2024.106579","DOIUrl":"10.1016/j.jsbmb.2024.106579","url":null,"abstract":"<div><p>Chronic stress refers to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated blood contents of ACTH and corticosterone (CORT), exhibiting significant adverse effects on health outcomes. Currently, natural polyphenol compounds are increasingly being explored as potential therapeutic agents and have been considered as a treatment option for a variety of stress-induced diseases. Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong health-beneficial properties. The study aimed to assess the potential protective effects of CUR on hepatic oxidative stress damage and abnormal lipid deposition in a chronic CORT-induced stress (CCIS) model in broilers. One hundred and twenty experimental broilers were randomly divided into 1) control group (CON), 2) CUR group (200 mg/kg feed), 3) CORT group (4 mg/kg BW CORT) and 4) CORT+CUR group (200 mg/kg feed plus 4 mg/kg BW CORT). The liver histology, glycolipid metabolism and oxidative stress were determined. In addition, qPCR was performed to identify shifts in genes expression. Compared with CON group, broilers under CCIS showed a decreased body weight, body weight gain and average daily gain, while dietary CUR significantly reversed these adverse effects. Furthermore, the plasma contents of TCH, TG, HDL-C, LDL-C, TP, GLB and AST were all significantly increased in CCIS broilers, while dietary CUR obviously alleviated the increase of TCH, HDL-C, LDL-C and AST, and relieved the hepatic lipid deposition disorder and liver injury. Moreover, CCIS significantly increased the contents of MDA in both liver and plasma, and decreased the content of plasma SOD, while CUR obviously reversed these changes, showing reduced oxidative stress damage. Finally, the mRNA expressions of FAS, ACC, SCD and the protein level of PPAR-γ were significantly increased, meanwhile the mRNA expression of lipolytic genes ACOX1, ATGL and CPT as well as two major intracellular antioxidant enzymes SOD1 and GPX1 were obviously decreased, while CUR effectively reversed these effects. These results showed that dietary CUR effectively alleviated CCIS-induced body weight loss, hepatic oxidative damage and lipid deposition disorder, suggesting the possible therapeutic effectiveness of CUR against hepatic damage and function abnormality caused by CCIS.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring neuron-specific steroid synthesis and DHEAS therapy in Alzheimer's disease","authors":"Hong-Yi Lin ,&nbsp;Yin-Hsun Feng ,&nbsp;Tzu-Jen Kao ,&nbsp;Hsien-Chung Chen ,&nbsp;Guan-Yuan Chen ,&nbsp;Chiung-Yuan Ko ,&nbsp;Tsung-I. Hsu","doi":"10.1016/j.jsbmb.2024.106585","DOIUrl":"10.1016/j.jsbmb.2024.106585","url":null,"abstract":"<div><p>Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Recent studies have suggested a potential role for steroid synthesis in AD pathology. This study investigated the co-localization of steroidogenic enzymes in neuronal cells, changes in enzyme expression in an AD mouse model, and steroid expressions in human AD samples. Additionally, we conducted a steroidomic metabolomics analysis and evaluated the effects of dehydroepiandrosterone sulfate (DHEAS) treatment in an AD mouse model. Immunofluorescence analysis revealed significant co-localization of cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and steroidogenic acute regulatory protein (StAR) proteins with α-synuclein in presynaptic neurons, suggesting active steroid synthesis in these cells. Conversely, such co-localization was absent in astrocytes. In the AD mouse model, a marked decrease in the expression of steroidogenic enzymes (Cyp11a1, Cyp17a1, Star) was observed, especially in areas with amyloid beta plaque accumulation. Human AD and MS brain tissues showed similar reductions in StAR and CYP17A1 expressions. Steroidomic analysis indicated a downregulation of key steroids in the serum of AD patients. DHEAS treatment in AD mice resulted in improved cognitive function and reduced Aβ accumulation. Our findings indicate a neuron-specific pathway for steroid synthesis, potentially playing a crucial role in AD pathology. The reduction in steroidogenic enzymes and key steroids in AD models and human samples suggests that impaired steroid synthesis is a feature of neurodegenerative diseases. The therapeutic potential of targeting steroid synthesis pathways, as indicated by the positive effects of DHEAS treatment, warrants further investigation.</p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}