Phytosterols are plant sterols that are important secondary plant metabolites with significant pharmacological properties. Their presence in the plant kingdom concerns many unrelated botanical families such as oleageneous plants and cereals. The structures of phytosterols evoke those of cholesterol. These molecules are composed of a sterane ring, also known as perhydrocyclopentanophenanthrene, along with a methyl or ethyl group at C-24 in their side chains, a hydroxyl group at C-3 on ring A, and one or two double bonds in the B ring. Phytosterols display different oxidation degrees at the sterane ring and at the side chain as well as varying numbers of carbons with complex stereochemistries. Fats and water solubilities of phytosterols have been achieved by physical, chemical and enzymatic esterifications to favor their bioavailability and to improve the sensory quality of food, and the efficiency of pharmaceutic and cosmetic products. This review aims to provide comprehensive information starting from the definition and structural classification of phytosterols, and exposes an update of their biogenic relationships. Next, the synthesis of phytosterol esters and their applications as well as their effective roles as hormone precursors are discussed. Finally, a concise exploration of the latest advancements in phytosterol / oxyphytosterols analysis techniques is provided, with a particular focus on modern hyphenated techniques.
{"title":"Current advances in phytosterol free forms and esters: Classification, biosynthesis, chemistry, and detection","authors":"Farid Khallouki , Wafa Zennouhi , Lhoussain Hajji , Mohamed Bourhia , Laila Benbacer , Bachir El Bouhali , Leila Rezig , Marc Poirot , Gérard Lizard","doi":"10.1016/j.steroids.2024.109520","DOIUrl":"10.1016/j.steroids.2024.109520","url":null,"abstract":"<div><div>Phytosterols are plant sterols that are important secondary plant metabolites with significant pharmacological properties. Their presence in the plant kingdom concerns many unrelated botanical families such as oleageneous plants and cereals. The structures of phytosterols evoke those of cholesterol. These molecules are composed of a sterane ring, also known as perhydrocyclopentanophenanthrene, along with a methyl or ethyl group at C-24 in their side chains, a hydroxyl group at C-3 on ring A, and one or two double bonds in the B ring. Phytosterols display different oxidation degrees at the sterane ring and at the side chain as well as varying numbers of carbons with complex stereochemistries. Fats and water solubilities of phytosterols have been achieved by physical, chemical and enzymatic esterifications to favor their bioavailability and to improve the sensory quality of food, and the efficiency of pharmaceutic and cosmetic products. This review aims to provide comprehensive information starting from the definition and structural classification of phytosterols, and exposes an update of their biogenic relationships. Next, the synthesis of phytosterol esters and their applications as well as their effective roles as hormone precursors are discussed. Finally, a concise exploration of the latest advancements in phytosterol / oxyphytosterols analysis techniques is provided, with a particular focus on modern hyphenated techniques.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109520"},"PeriodicalIF":2.1,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diosgenin, a bioactive molecule; is one of the deeply explored saponin with a wide spectrum of benefits against various ailments. The extraction and yield enhancement of diosgenin from a wide range of naturally occurring medicinal products has always been a challenging task for its commercial usage. The current research work envisages the use of a novel resin to maximize the yield of diosgenin. The extracted diosgenin was characterized using modern techniques. The current method qualifies for the extraction of diosgenin at a large scale making it a commercially viable technique.
{"title":"A sustainable approach towards extraction of diosgenin from fenugreek seeds using polystyrene/divinyl benzene resin","authors":"Sharavan Kumar , B.M. Praveen , Aralihalli Sudhakara","doi":"10.1016/j.steroids.2024.109519","DOIUrl":"10.1016/j.steroids.2024.109519","url":null,"abstract":"<div><div>Diosgenin, a bioactive molecule; is one of the deeply explored saponin with a wide spectrum of benefits against various ailments. The extraction and yield enhancement of diosgenin from a wide range of naturally occurring medicinal products has always been a challenging task for its commercial usage. The current research work envisages the use of a novel resin to maximize the yield of diosgenin. The extracted diosgenin was characterized using modern techniques. The current method qualifies for the extraction of diosgenin at a large scale making it a commercially viable technique.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109519"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.steroids.2024.109517
Lawrence D. Harris , Roselis A. Landaeta Aponte , Wanting Jiao , Scott A. Cameron , Alex Weymouth-Wilson , Richard H. Furneaux , Benjamin J. Compton , Andreas Luxenburger
Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure–activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties. Among the many steroidal derivatisations reported, the formation of endocyclic azasteroids appeals due to their potential to deliver altered biological responses with minimal change to the steroidal superstructure. Here, we report the synthesis of 3-aza-obeticholic acid (6) via a regioconvergent route. Ammoniolysis of lactones, formed from an m-CPBA-mediated Baeyer-Villiger reaction on a 3-keto-OCA derivative, furnished protected intermediate amido-alcohols which were separately elaborated to amino-alcohols via Hofmann degradation with BAIB. Upon individual N-Boc-protection, these underwent annulation to the 3-aza-A-ring when subjected to either mesylation or a Dess-Martin oxidation/hydrogenation sequence. Global deprotection of the 3-aza-intermediate delivered 3-aza-OCA in ten steps and an overall yield of up to 19%.
{"title":"An efficient regioconvergent synthesis of 3-aza-obeticholic acid","authors":"Lawrence D. Harris , Roselis A. Landaeta Aponte , Wanting Jiao , Scott A. Cameron , Alex Weymouth-Wilson , Richard H. Furneaux , Benjamin J. Compton , Andreas Luxenburger","doi":"10.1016/j.steroids.2024.109517","DOIUrl":"10.1016/j.steroids.2024.109517","url":null,"abstract":"<div><div>Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure–activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties. Among the many steroidal derivatisations reported, the formation of endocyclic azasteroids appeals due to their potential to deliver altered biological responses with minimal change to the steroidal superstructure. Here, we report the synthesis of 3-aza-obeticholic acid (<strong>6</strong>) <em>via</em> a regioconvergent route. Ammoniolysis of lactones, formed from an <em>m</em>-CPBA-mediated Baeyer-Villiger reaction on a 3-keto-OCA derivative, furnished protected intermediate amido-alcohols which were separately elaborated to amino-alcohols <em>via</em> Hofmann degradation with BAIB. Upon individual <em>N</em>-Boc-protection, these underwent annulation to the 3-aza-A-ring when subjected to either mesylation or a Dess-Martin oxidation/hydrogenation sequence. Global deprotection of the 3-aza-intermediate delivered 3-aza-OCA in ten steps and an overall yield of up to 19%.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109517"},"PeriodicalIF":2.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.steroids.2024.109518
Ankan Sinha , Vishal Kumar Deb , Abhijit Datta , Satpal Yadav , Ashish Phulkar , Suman Adhikari
Anabolic-androgenic steroids (AASs), more correctly termed “steroidal androgens”, are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have long been employed as performance-enhancing substances, primarily among recreational athletes and some professionals. While their short-term effects on muscle physiology are well-documented, the long-term health consequences remain inadequately understood. A key finding is the disruption of hormone production, leading to reversible and irreversible changes, particularly with prolonged use. While debate exists over the prevalence of adverse effects, studies suggest a spectrum of somatic and psychiatric consequences, highlighting the need for improved understanding and prevention strategies. AASs are not only affect muscle structure but also influence mood, behavior, and body image, potentially exacerbating substance dependence and psychological distress. Liver alterations are a prominent concern, with oxidative stress implicated in AAS-induced hepatotoxicity. Reproductive complications, including gonadal atrophy and infertility, are common, alongside virilization and feminization effects in both genders. Cardiovascular effects are particularly worrisome, with AASs implicated in hypertension, dyslipidemia, and increased thrombotic risk, contributing to cardiovascular morbidity and mortality. Moreover, AASs may enhance cancer risks, potentially accelerating carcinogenesis in various tissues, including the prostate. The review emphasizes the need for comprehensive public health initiatives to mitigate harm, including harm minimization strategies, routine health screenings, and targeted interventions for AAS users. Understanding the complex interplay of biological mechanisms and systemic effects is crucial for informing clinical management and preventive measures. This review also examines the biological impact of AASs on human muscles, detailing mechanisms of action, chemistry, and associated health risks such as liver damage, cardiovascular disease, and endocrine dysfunction.
{"title":"Evaluation of structural features of anabolic-androgenic steroids: entanglement for organ-specific toxicity","authors":"Ankan Sinha , Vishal Kumar Deb , Abhijit Datta , Satpal Yadav , Ashish Phulkar , Suman Adhikari","doi":"10.1016/j.steroids.2024.109518","DOIUrl":"10.1016/j.steroids.2024.109518","url":null,"abstract":"<div><div>Anabolic-androgenic steroids (AASs), more correctly termed “steroidal androgens”, are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have long been employed as performance-enhancing substances, primarily among recreational athletes and some professionals. While their short-term effects on muscle physiology are well-documented, the long-term health consequences remain inadequately understood. A key finding is the disruption of hormone production, leading to reversible and irreversible changes, particularly with prolonged use. While debate exists over the prevalence of adverse effects, studies suggest a spectrum of somatic and psychiatric consequences, highlighting the need for improved understanding and prevention strategies. AASs are not only affect muscle structure but also influence mood, behavior, and body image, potentially exacerbating substance dependence and psychological distress. Liver alterations are a prominent concern, with oxidative stress implicated in AAS-induced hepatotoxicity. Reproductive complications, including gonadal atrophy and infertility, are common, alongside virilization and feminization effects in both genders. Cardiovascular effects are particularly worrisome, with AASs implicated in hypertension, dyslipidemia, and increased thrombotic risk, contributing to cardiovascular morbidity and mortality. Moreover, AASs may enhance cancer risks, potentially accelerating carcinogenesis in various tissues, including the prostate. The review emphasizes the need for comprehensive public health initiatives to mitigate harm, including harm minimization strategies, routine health screenings, and targeted interventions for AAS users. Understanding the complex interplay of biological mechanisms and systemic effects is crucial for informing clinical management and preventive measures. This review also examines the biological impact of AASs on human muscles, detailing mechanisms of action, chemistry, and associated health risks such as liver damage, cardiovascular disease, and endocrine dysfunction.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109518"},"PeriodicalIF":2.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1016/j.steroids.2024.109516
Yu Pan , Chunxia Yang , Yan Sun, Shenmin Zhang, Tongmin Xue, Feng Li, Dan Fu
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.
{"title":"SPRY4 regulates ERK1/2 phosphorylation to affect oxidative stress and steroidogenesis in polycystic ovary syndrome","authors":"Yu Pan , Chunxia Yang , Yan Sun, Shenmin Zhang, Tongmin Xue, Feng Li, Dan Fu","doi":"10.1016/j.steroids.2024.109516","DOIUrl":"10.1016/j.steroids.2024.109516","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist <em>tert</em>-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with <em>tert</em>-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109516"},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds 2, 4 and 5 inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of 1, 2, 3, 4 and 5 against the protein 1F9F were −8.01, −8.70, −9.43, −9.58 and −9.75 kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (1). ADMET analyses of all derivatives have also been carried out.
{"title":"Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis","authors":"Astha Yadav , Anmol Verma , Saurabh Kumar Singh , Rohit Prakash , Sanjay Srivastava , Arun Sethi , Ranvijay Pratap Singh","doi":"10.1016/j.steroids.2024.109515","DOIUrl":"10.1016/j.steroids.2024.109515","url":null,"abstract":"<div><div>In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds <strong>2</strong>, <strong>4</strong> and <strong>5</strong> inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of <strong>1</strong>, <strong>2</strong>, <strong>3</strong>, <strong>4</strong> and <strong>5</strong> against the protein 1F9F were −<strong>8.01</strong>, <strong>−8.70</strong>, <strong>−9.43</strong>, <strong>−9.58</strong> and <strong>−9.75</strong> kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (<strong>1</strong>). ADMET analyses of all derivatives have also been carried out.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109515"},"PeriodicalIF":2.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.steroids.2024.109511
Alice W. Njue , Josiah Omolo , Ryan S. Ramos , Cleydson B.R. Santos , Njogu M. Kimani
In this study, five steroid compounds were isolated from the fruiting bodies mushroom Trametes versicolor. The compounds, 9,19-cyclolanostane-3,29-diol (3), ergosta-7,22-dien-3-acetate (4), and ergosta-8(14),22-dien-3β,5α,6β,7α-tetrol (5), were identified from T. versicolor for the first time. The five compounds were evaluated for their activity against cancer cell lines. Compound 5α,8α–epidioxyergosta-6,22-dien-3β-ol (1) was found to be the most effective against most of the cancer cell lines tested. In silico studies showed that compound 1 has good binding affinities to different cancer targets, namely cyclin-dependent kinase 2 (cdk2), human cyclin-dependent kinase 6 (cdk6), Human Topo IIa ATPase/AMP-PNP, anti-apoptotic protein Bcl-2, and Vegfr-2. It’s also druglike based on Lipinski’s rule of five and it’s ADME/Tox properties. Therefore, compound 1 is a good candidate in the management of cancer. These results further show that T. versicolor is a potential source of drugs or drug leads for cancer treatment.
{"title":"Ergostanes from the mushroom Trametes versicolor and their cancer cell inhibition: In vitro and in silico evaluation","authors":"Alice W. Njue , Josiah Omolo , Ryan S. Ramos , Cleydson B.R. Santos , Njogu M. Kimani","doi":"10.1016/j.steroids.2024.109511","DOIUrl":"10.1016/j.steroids.2024.109511","url":null,"abstract":"<div><div>In this study, five steroid compounds were isolated from the fruiting bodies mushroom <em>Trametes versicolor.</em> The compounds, 9,19-cyclolanostane-3,29-diol (<strong>3</strong>), ergosta-7,22-dien-3-acetate (<strong>4</strong>), and ergosta-8(14),22-dien-3β,5α,6β,7α-tetrol (<strong>5</strong>), were identified from <em>T. versicolor</em> for the first time. The five compounds were evaluated for their activity against cancer cell lines. Compound 5α,8α–epidioxyergosta-6,22-dien-3β-ol (<strong>1</strong>) was found to be the most effective against most of the cancer cell lines tested. <em>In silico</em> studies showed that compound <strong>1</strong> has good binding affinities to different cancer targets, namely cyclin-dependent kinase 2 (cdk2), human cyclin-dependent kinase 6 (cdk6), Human Topo IIa ATPase/AMP-PNP, anti-apoptotic protein Bcl-2, and Vegfr-2. It’s also druglike based on Lipinski’s rule of five and it’s ADME/Tox properties. Therefore, compound <strong>1</strong> is a good candidate in the management of cancer. These results further show that <em>T. versicolor</em> is a potential source of drugs or drug leads for cancer treatment.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109511"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.steroids.2024.109513
Leila Mirzaeian , Khadijeh Bahrehbar , Mandana Emamdoust , Masoumeh Amiri , Maryam Azari , Mohammad Taghi Ghorbanian
Objective
Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult brain. Sex hormones play an essential role in the development of the brain. The aim of this study was to evaluate the neurogenic changes in the brain at different phases of the estrous cycle in adult mice.
Materials and methods
Female NMRI mice were divided into four groups: 1- Estrous, 2- Proestrous, 3- Metestrous, and 4- Diestrous. Different stages of the estrous cycle were determined by staining of vaginal smears. The level of estrogen, progesterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones was evaluated by the enzyme-linked immunosorbent assay (ELISA) method. The expression of brain-derived neurotrophic factor) BDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF)) genes in hippocampal and the expression of glial fibrillary acidic protein (GFAP) in subventricular zone (SVZ) tissue were evaluated.
Results
The serum estrogen and FSH increased significantly in Proestrous group (p < 0.001). Also, progesterone and prolactin hormones were significantly increased in the Diaestrus group (p < 0.001). The expression levels of BDNF, NGF, and CNTF significantly increased in the hippocampal tissue of Proestrous and Diaestrus groups (p < 0.001). The number of GFAP+ cells in SVZ of the Proestrous and Diestrous groups had a significant increase (p < 0.05, p < 0.01, p < 0.001).
Conclusion
Our data showed that Changes in sex hormones, especially estrogen in the estrous cycle, can cause the production of new neurons and astrocytes in the hippocampus and SVZ. Therefore, the increase in neurotrophic factors in the Proestrus and Diestrus leads to neurogenesis in adult mice brains.
{"title":"Investigating the influence of estrous cycle-dependent hormonal changes on neurogenesis in adult mice","authors":"Leila Mirzaeian , Khadijeh Bahrehbar , Mandana Emamdoust , Masoumeh Amiri , Maryam Azari , Mohammad Taghi Ghorbanian","doi":"10.1016/j.steroids.2024.109513","DOIUrl":"10.1016/j.steroids.2024.109513","url":null,"abstract":"<div><h3>Objective</h3><div>Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult brain. Sex hormones play an essential role in the development of the brain. The aim of this study was to evaluate the neurogenic changes in the brain at different phases of the estrous cycle in adult mice.</div></div><div><h3>Materials and methods</h3><div>Female NMRI mice were divided into four groups: 1- Estrous, 2- Proestrous, 3- Metestrous, and 4- Diestrous. Different stages of the estrous cycle were determined by staining of vaginal smears. The level of estrogen, progesterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones was evaluated by the enzyme-linked immunosorbent assay (ELISA) method. The expression of brain-derived neurotrophic factor) <em>BDNF</em>)<em>,</em> nerve growth factor (<em>NGF</em>)<em>,</em> ciliary neurotrophic factor<!--> <!-->(<em>CNTF</em>)) genes in hippocampal and the expression of glial fibrillary acidic protein (GFAP) in subventricular zone (SVZ) tissue were evaluated.</div></div><div><h3>Results</h3><div>The serum estrogen and FSH increased significantly in Proestrous group (p < 0.001). Also, progesterone and prolactin hormones were significantly increased in the Diaestrus group (p < 0.001). The expression levels of <em>BDNF</em>, <em>NGF,</em> and <em>CNTF</em> significantly increased in the hippocampal tissue of Proestrous and Diaestrus groups (p < 0.001). The number of GFAP<sup>+</sup> cells in SVZ of the Proestrous and Diestrous groups had a significant increase (p < 0.05, p < 0.01, p < 0.001).</div></div><div><h3>Conclusion</h3><div>Our data showed that Changes in sex hormones, especially estrogen in the estrous cycle, can cause the production of new neurons and astrocytes in the hippocampus and SVZ. Therefore, the increase in neurotrophic factors in the Proestrus and Diestrus leads to neurogenesis in adult mice brains.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109513"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.steroids.2024.109514
Ekramy M. Elmorsy , Ayat B. Al-Ghafari , Huda A. Al Doghaither , Manal S. Fawzy , Shaimaa A. Shehata
Despite the known therapeutic uses of dexamethasone (DEX), the specific mechanisms underlying its neurotoxic effects in neuronal cells, particularly in undifferentiated human neuroblastoma (SH-SY5Y) cells, remain inadequately understood. This study aims to elucidate these mechanisms, emphasizing bioenergetics, oxidative stress, and apoptosis, thereby providing novel insights into the cellular vulnerabilities induced by chronic DEX exposure. The findings revealed significant reductions in cell viability, altered membrane integrity with LDH leakage, decreased intracellular ATP production, and the electron transport chain complexes I and III activity inhibition. DEX significantly increased the release of the reactive species and peroxidation of lipids, as well as of Nrf2 expression. At the same time, it simultaneously led to a decline in the activities of the antioxidant catalase and superoxide dismutase enzymes, along with a depletion of glutathione reserves. The apoptosis process was exhibited by a significant elevation of caspases 3 and 8 activities with overexpression of mRNA BAX, inhibition of BCL-2, and a significant upregulation of the BAX/BCL-2 ratio. Assessment of neuronal development genes (GAP43, CAMK2A, CAMK2B, TUBB3, and Wnts) by quantitative PCR assay showed increased expression of CAMK2A, CAMK2B, and Wnt3a with a significant reduction in GAP43 mRNA levels. Collectively, this study proved that DEX was cytotoxic to SH-SY5Y via bioenergetic disruption, mitochondrial dysfunction, oxidative stress, and apoptosis.
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Pub Date : 2024-09-14DOI: 10.1016/j.steroids.2024.109512
Foram K. Ravat, Janki R. Goswami, Sneha M. Nair, Kashyap N. Thummar
Introduction
Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting reproductive-aged women worldwide. Characterized by irregular menstruation, signs of hyperandrogenism, polycystic ovaries via ultrasound ovarian dysfunction.
Area covered
The review delves into the intricate pathophysiological mechanisms underlying the syndrome. Dysregulation of the hypothalamic-pituitary-ovarian axis, IR, obesity, and hyperandrogenism contribute to anovulation and follicular dysfunction which is associated with gut dysbiosis, bile metabolites, and an unhealthy diet.
Metabolomics and genomics analyses offer insights into the metabolism of bile acids (BAs) and gut microbiota dysbiosis in PCOS. BAs, crucial for metabolic regulation, are influenced by microbes, impacting hormonal balance. Disruptions in gut microbiota contribute to hormonal dysregulation. Interconnected pathways involving BAs and gut microbiota are pivotal in PCOS. Therapeutic implications include a healthy diet, exercise, and interventions targeting gut microbiota modulation and BAs metabolite to alleviate PCOS symptoms and improve metabolic health.
Conclusion
PCOS requires a multifaceted, multidisciplinary approach for effective management, including lifestyle changes, medications, and emerging therapies. Tailored strategies considering individual needs and personalized treatment plans are crucial for successful PCOS management. Despite existing knowledge, comprehensive investigations are needed to bridge research gaps and discern the interconnected pathways linking the development of PCOS and the gut-bile axis which are interconnected with metabolic disorders and the development of PCOS. Gut microbiota and hormonal regulation offer promising avenues for innovative therapeutic strategies aimed at addressing the root causes of PCOS and improving patient outcomes.
导言多囊卵巢综合征（PCOS）是影响全球育龄妇女的一种常见内分泌和代谢疾病。其特征是月经不调、高雄激素征兆、多囊卵巢（通过超声波检查卵巢功能异常）。下丘脑-垂体-卵巢轴调节失调、IR、肥胖和高雄激素导致无排卵和卵泡功能障碍，而这与肠道菌群失调、胆汁代谢产物和不健康饮食有关。代谢组学和基因组学分析提供了有关多囊卵巢综合征中胆汁酸（BAs）代谢和肠道微生物群失调的见解。胆汁酸对新陈代谢的调节至关重要，它受到微生物的影响，从而影响荷尔蒙平衡。肠道微生物群紊乱会导致荷尔蒙失调。涉及生物碱和肠道微生物群的相互关联途径在多囊卵巢综合症中至关重要。治疗意义包括健康饮食、运动以及针对肠道微生物群调节和 BAs 代谢物的干预措施，以减轻 PCOS 症状并改善代谢健康。考虑个人需求的定制策略和个性化治疗计划是成功控制多囊卵巢综合症的关键。尽管已有相关知识，但仍需进行全面调查，以弥补研究差距，并找出多囊卵巢综合症的发病与肠道胆汁轴之间的相互关联途径，而肠道胆汁轴与代谢紊乱和多囊卵巢综合症的发病是相互关联的。肠道微生物群和荷尔蒙调节为旨在解决多囊卵巢综合症的根本原因和改善患者预后的创新治疗策略提供了前景广阔的途径。
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