Pub Date : 2025-01-09DOI: 10.1016/j.steroids.2025.109560
Jair García-Méndez, Adolfo López-Torres, María A Fernández-Herrera
Bile acid esters and their derivatives hold significant interest due to their applications in fields such as supramolecular chemistry, biomedicine, and nanomaterials. This study revisits the synthesis and characterization of esters derived from cholic, deoxycholic, and lithocholic acids using short-chain alcohols in combination with microwave-assisted heating. The synthesized esters were analyzed for their potential as gel-forming agents, and their organogelation properties were evaluated. Microwave-assisted synthesis offers rapid and efficient esterification, leading to high yields with improved selectivity. The organogels were characterized through techniques such as differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), revealing distinct structural and thermal properties. The study highlights the potential of these bile acid esters in materials science and supramolecular chemistry, contributing to the development of novel functional materials.
{"title":"Improved synthesis and characterization of bile acid esters: Organogelation and supramolecular properties.","authors":"Jair García-Méndez, Adolfo López-Torres, María A Fernández-Herrera","doi":"10.1016/j.steroids.2025.109560","DOIUrl":"10.1016/j.steroids.2025.109560","url":null,"abstract":"<p><p>Bile acid esters and their derivatives hold significant interest due to their applications in fields such as supramolecular chemistry, biomedicine, and nanomaterials. This study revisits the synthesis and characterization of esters derived from cholic, deoxycholic, and lithocholic acids using short-chain alcohols in combination with microwave-assisted heating. The synthesized esters were analyzed for their potential as gel-forming agents, and their organogelation properties were evaluated. Microwave-assisted synthesis offers rapid and efficient esterification, leading to high yields with improved selectivity. The organogels were characterized through techniques such as differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), revealing distinct structural and thermal properties. The study highlights the potential of these bile acid esters in materials science and supramolecular chemistry, contributing to the development of novel functional materials.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109560"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967028","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 : 2024-12-30DOI: 10.1016/j.steroids.2024.109559
Yechiel Atias, Tavor Ben-Zeev, Chagai Levi, Lior Binman, Jay R Hoffman
Purpose: This study examined the effect of resistance training (RT) by itself and in combination with supraphysiological administration of nandrolone decanoate (ND) on the inflammatory, apoptotic, and oxidative stress response in cardiac tissue. The effect of the training and androgen intervention on adiponectin expression, a potential cardio protectant was also examined.
Methods: Forty male C57Bl/6J mice, 3 months of age were randomized into four groups (n = 10 per group). Two groups of animals performed a 3-day per week RT program for 7-weeks, while the other two groups remained sedentary (SED). The RT and SED animals were further randomized into an androgen group (RTA and SEDA, respectively) or a sham group (RTS and SEDS, respectively). Animals in the RTA and SEDA groups received 38-mg·kg-1 injected once per week. Mice from RTS and SEDS received sham injections.
Results: Main effects for group indicated that RT resulted in significant elevations in NFκβ (p < 0.001), glutamine peroxidase (GPX) (p = 0.007) and adiponectin (p < 0.001). Main effects for treatment indicated that ND administration resulted in greater elevations in NFκβ (p = 0.01) and TNF-α (p = 0.017). In addition, TNF-α expression was greater in RTA compared to RETS (p = 0.006) and the adiponectin response in RTA was greater (p's < 0.05) than all other groups. A significant correlation was noted between average training volume during the RT program and GPX expression (r = 0.716, p < 0.001).
Conclusion: Results indicate that RT and ND administration can increase markers of apoptosis and inflammation. Elevations in adiponectin expression suggest that it may act as a compensatory mechanism supporting cardiovascular health.
{"title":"The effect of resistance training and nandrolone decanoate administration on cardiac tissue in mice.","authors":"Yechiel Atias, Tavor Ben-Zeev, Chagai Levi, Lior Binman, Jay R Hoffman","doi":"10.1016/j.steroids.2024.109559","DOIUrl":"https://doi.org/10.1016/j.steroids.2024.109559","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined the effect of resistance training (RT) by itself and in combination with supraphysiological administration of nandrolone decanoate (ND) on the inflammatory, apoptotic, and oxidative stress response in cardiac tissue. The effect of the training and androgen intervention on adiponectin expression, a potential cardio protectant was also examined.</p><p><strong>Methods: </strong>Forty male C57Bl/6J mice, 3 months of age were randomized into four groups (n = 10 per group). Two groups of animals performed a 3-day per week RT program for 7-weeks, while the other two groups remained sedentary (SED). The RT and SED animals were further randomized into an androgen group (RTA and SEDA, respectively) or a sham group (RTS and SEDS, respectively). Animals in the RTA and SEDA groups received 38-mg·kg<sup>-1</sup> injected once per week. Mice from RTS and SEDS received sham injections.</p><p><strong>Results: </strong>Main effects for group indicated that RT resulted in significant elevations in NFκβ (p < 0.001), glutamine peroxidase (GPX) (p = 0.007) and adiponectin (p < 0.001). Main effects for treatment indicated that ND administration resulted in greater elevations in NFκβ (p = 0.01) and TNF-α (p = 0.017). In addition, TNF-α expression was greater in RTA compared to RETS (p = 0.006) and the adiponectin response in RTA was greater (p's < 0.05) than all other groups. A significant correlation was noted between average training volume during the RT program and GPX expression (r = 0.716, p < 0.001).</p><p><strong>Conclusion: </strong>Results indicate that RT and ND administration can increase markers of apoptosis and inflammation. Elevations in adiponectin expression suggest that it may act as a compensatory mechanism supporting cardiovascular health.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109559"},"PeriodicalIF":2.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915689","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 : 2024-12-30DOI: 10.1016/j.steroids.2024.109558
Shubhi Yadav, Shailesh Dadge, Richa Garg, Umesh K Goand, Arun Agarwal, Divya Chauhan, Jiaur R Gayen
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder associated with insulin resistance (IR) and hyperandrogenism. IR plays a crucial role in the etiology of PCOS. An insulin-sensitizing agent like metformin is most commonly used as an off-label drug for the treatment of PCOS. PSTi8 (a pancreastatin inhibitor) is known as a promising therapeutic insulin-sensitizing agent for the treatment of IR in metabolic diseases. Thus, this study evaluates the insulin-sensitizing effects of PSTi8 compared to metformin on IR, hyperandrogenism, ovarian, and metabolic dysfunction in a PCOS model. To induce PCOS, rats were administered letrozole at a dose of 2 mg/kg via oral administration and fed a 60 % high-fat diet. Metformin and PSTi8 lowered serum insulin, testosterone, luteinizing hormone (LH) levels, and the LH/follicle-stimulating hormone ratio in the blood serum and improved steroidogenic gene expression in the PCOS ovaries. Both treatments increased the levels of sex hormone-binding globulin and estrogen hormone. Metformin and PSTi8 restore ovarian and uterine histomorphometry and improve the estrous cycle in PCOS rats. Metformin and PSTi8 treatments also improve blood glucose level and increase insulin sensitivity, inflammation, reactive oxygen species accumulation, lipid parameters, body weight, and fat mass in PCOS rats. This study revealed that PSTi8 is as helpful as metformin in decreasing hyperandrogenism by improving insulin sensitivity, free testosterone level and restoring disturbed reproductive and metabolic parameters in PCOS rats. PSTi8 has potential to serve as a therapeutic molecule for preventing IR induced by a western diet in PCOS.
{"title":"Pancreastatin inhibitor PSTi8 improves ovarian health in Letrozole-HFD induced PCOS rats by ameliorating metabolic and reproductive parameters.","authors":"Shubhi Yadav, Shailesh Dadge, Richa Garg, Umesh K Goand, Arun Agarwal, Divya Chauhan, Jiaur R Gayen","doi":"10.1016/j.steroids.2024.109558","DOIUrl":"10.1016/j.steroids.2024.109558","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder associated with insulin resistance (IR) and hyperandrogenism. IR plays a crucial role in the etiology of PCOS. An insulin-sensitizing agent like metformin is most commonly used as an off-label drug for the treatment of PCOS. PSTi8 (a pancreastatin inhibitor) is known as a promising therapeutic insulin-sensitizing agent for the treatment of IR in metabolic diseases. Thus, this study evaluates the insulin-sensitizing effects of PSTi8 compared to metformin on IR, hyperandrogenism, ovarian, and metabolic dysfunction in a PCOS model. To induce PCOS, rats were administered letrozole at a dose of 2 mg/kg via oral administration and fed a 60 % high-fat diet. Metformin and PSTi8 lowered serum insulin, testosterone, luteinizing hormone (LH) levels, and the LH/follicle-stimulating hormone ratio in the blood serum and improved steroidogenic gene expression in the PCOS ovaries. Both treatments increased the levels of sex hormone-binding globulin and estrogen hormone. Metformin and PSTi8 restore ovarian and uterine histomorphometry and improve the estrous cycle in PCOS rats. Metformin and PSTi8 treatments also improve blood glucose level and increase insulin sensitivity, inflammation, reactive oxygen species accumulation, lipid parameters, body weight, and fat mass in PCOS rats. This study revealed that PSTi8 is as helpful as metformin in decreasing hyperandrogenism by improving insulin sensitivity, free testosterone level and restoring disturbed reproductive and metabolic parameters in PCOS rats. PSTi8 has potential to serve as a therapeutic molecule for preventing IR induced by a western diet in PCOS.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109558"},"PeriodicalIF":2.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915687","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 : 2024-12-28DOI: 10.1016/j.steroids.2024.109556
Lucas D Ferreira, Bruno A Aguilar, João V M Bernal, Kelly Y Melo, Maria E Gerolim, Tallys E V Paixão, Danielle A Tiburcio, Hugo C D Souza
Introduction: The use of anabolic steroids is widely adopted for aesthetic purposes and sports performance. In supraphysiological doses, they can impair various physiological systems. However, we know little about their effects on the heart, especially when combined with strength training. In this regard, we investigated the effects of nandrolone decanoate at supraphysiological doses, combined with strength training, on cardiac hemodynamic, morphological, and functional parameters using different approaches.
Methods: Male Wistar rats (N = 64, 18 weeks old) were divided into two groups (N = 32): vehicle-treated (VEH; peanut oil, 0.2 ml/kg) and nandrolone decanoate-treated (NAN, 5 mg/kg). Half of each group (N = 16) underwent strength training following a progressive load stair protocol three times per week for 12 weeks (T-VEH and T-NAN). All groups had their cardiac hemodynamic, morphological, and functional parameters recorded through two-dimensional echocardiography, while coronary perfusion pressure and left ventricular pressure (LVP) were measured using the Langendorff technique in isolated hearts.
Results: Both nandrolone decanoate-treated groups showed higher values of relative cardiac mass, interventricular septum thickness, and final diastolic and systolic diameters of the left ventricle compared to vehicle-treated groups (VEH and T-VEH). The NAN group exhibited reductions in coronary perfusion pressure, LVP, and maximum and minimum dP/dT compared to the VEH and T-VEH groups, while the T-NAN group showed reduced values for coronary perfusion pressure and LVP compared to the VEH group.
Conclusions: Nandrolone decanoate treatment at supraphysiological doses reduced left ventricular performance. In turn, strength training appeared to provide minimal attenuation of these impairments.
{"title":"Chronic treatment with nandrolone decanoate reduces left ventricular contractile response even when combined with strength training.","authors":"Lucas D Ferreira, Bruno A Aguilar, João V M Bernal, Kelly Y Melo, Maria E Gerolim, Tallys E V Paixão, Danielle A Tiburcio, Hugo C D Souza","doi":"10.1016/j.steroids.2024.109556","DOIUrl":"10.1016/j.steroids.2024.109556","url":null,"abstract":"<p><strong>Introduction: </strong>The use of anabolic steroids is widely adopted for aesthetic purposes and sports performance. In supraphysiological doses, they can impair various physiological systems. However, we know little about their effects on the heart, especially when combined with strength training. In this regard, we investigated the effects of nandrolone decanoate at supraphysiological doses, combined with strength training, on cardiac hemodynamic, morphological, and functional parameters using different approaches.</p><p><strong>Methods: </strong>Male Wistar rats (N = 64, 18 weeks old) were divided into two groups (N = 32): vehicle-treated (VEH; peanut oil, 0.2 ml/kg) and nandrolone decanoate-treated (NAN, 5 mg/kg). Half of each group (N = 16) underwent strength training following a progressive load stair protocol three times per week for 12 weeks (T-VEH and T-NAN). All groups had their cardiac hemodynamic, morphological, and functional parameters recorded through two-dimensional echocardiography, while coronary perfusion pressure and left ventricular pressure (LVP) were measured using the Langendorff technique in isolated hearts.</p><p><strong>Results: </strong>Both nandrolone decanoate-treated groups showed higher values of relative cardiac mass, interventricular septum thickness, and final diastolic and systolic diameters of the left ventricle compared to vehicle-treated groups (VEH and T-VEH). The NAN group exhibited reductions in coronary perfusion pressure, LVP, and maximum and minimum dP/dT compared to the VEH and T-VEH groups, while the T-NAN group showed reduced values for coronary perfusion pressure and LVP compared to the VEH group.</p><p><strong>Conclusions: </strong>Nandrolone decanoate treatment at supraphysiological doses reduced left ventricular performance. In turn, strength training appeared to provide minimal attenuation of these impairments.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109556"},"PeriodicalIF":2.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907711","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}
Physalis alkekengi L. is recognized as a significant source of various secondary metabolites, particularly C28 steroidal lactones known as withanolides and physalins, renowned for their therapeutic properties with a rich history in traditional medicine. In this study, we characterized the sequences of key downstream genes (PaFPPS, PaSQS, PaSQE, PaCAS, PaHYD1, and PaDWF5-1) involved in the biosynthesis of withanolides, marking the first characterization of these genes in P. alkekengi. Our findings revealed highly conserved amino acid sequences in P. alkekengi, with maximum similarity observed with Withania somnifera. Notably, essential domains crucial for enzyme function were preserved in P. alkekengi, indicating conserved enzyme activity. Comparative analysis of secondary structures, 3D topologies, and evolutionary studies supported ancestral homology. Investigations into the differential gene expression of these genes across seven tissues (young leaves, stems, roots, flowers, mature green fruit, breaker fruit, and red ripe fruit) highlighted higher expression levels in P. alkekengi leaves. These gene expression patterns were corroborated by phytochemical analyses using chromatographic techniques. High-Performance Liquid Chromatography (HPLC) confirmed the production of two key withanolides, withanolide A and withanone, in P. alkekengi, with maximum production observed in leaves and flowers. These findings suggest that P. alkekengi holds promise as an alternative to W. somnifera for large-scale industrial production of withanolides, particularly withanolide A. Using P. alkekengi eliminates the need to sacrifice the plant, which is typically required in traditional extraction methods from the roots of W. somnifera.
{"title":"Structural and functional characterization of genes and enzymes involved in withanolide biosynthesis in Physalis alkekengi L.","authors":"Swati Gupta, Bashir Akhlaq Akhoon, Deepak Sharma, Deepika Singh, Sanjana Kaul, Manoj Kumar Dhar","doi":"10.1016/j.steroids.2024.109557","DOIUrl":"https://doi.org/10.1016/j.steroids.2024.109557","url":null,"abstract":"<p><p>Physalis alkekengi L. is recognized as a significant source of various secondary metabolites, particularly C<sub>28</sub> steroidal lactones known as withanolides and physalins, renowned for their therapeutic properties with a rich history in traditional medicine. In this study, we characterized the sequences of key downstream genes (PaFPPS, PaSQS, PaSQE, PaCAS, PaHYD1, and PaDWF5-1) involved in the biosynthesis of withanolides, marking the first characterization of these genes in P. alkekengi. Our findings revealed highly conserved amino acid sequences in P. alkekengi, with maximum similarity observed with Withania somnifera. Notably, essential domains crucial for enzyme function were preserved in P. alkekengi, indicating conserved enzyme activity. Comparative analysis of secondary structures, 3D topologies, and evolutionary studies supported ancestral homology. Investigations into the differential gene expression of these genes across seven tissues (young leaves, stems, roots, flowers, mature green fruit, breaker fruit, and red ripe fruit) highlighted higher expression levels in P. alkekengi leaves. These gene expression patterns were corroborated by phytochemical analyses using chromatographic techniques. High-Performance Liquid Chromatography (HPLC) confirmed the production of two key withanolides, withanolide A and withanone, in P. alkekengi, with maximum production observed in leaves and flowers. These findings suggest that P. alkekengi holds promise as an alternative to W. somnifera for large-scale industrial production of withanolides, particularly withanolide A. Using P. alkekengi eliminates the need to sacrifice the plant, which is typically required in traditional extraction methods from the roots of W. somnifera.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"109557"},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898305","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 : 2024-12-19DOI: 10.1016/j.steroids.2024.109555
Nuo Chen, Yunqiang Wu, Huamao Wei, Shuai Zhi, Liwei Liu
Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact. This review consolidates recent progress on bufotalin's structure, activity, cytotoxic mechanisms, and synthetic methodologies, offering a foundation for further development as an innovative chemotherapy agent.
{"title":"The advancement of structure, bioactivity, mechanism, and synthesis of bufotalin.","authors":"Nuo Chen, Yunqiang Wu, Huamao Wei, Shuai Zhi, Liwei Liu","doi":"10.1016/j.steroids.2024.109555","DOIUrl":"10.1016/j.steroids.2024.109555","url":null,"abstract":"<p><p>Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact. This review consolidates recent progress on bufotalin's structure, activity, cytotoxic mechanisms, and synthetic methodologies, offering a foundation for further development as an innovative chemotherapy agent.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109555"},"PeriodicalIF":2.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872833","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 : 2024-12-18DOI: 10.1016/j.steroids.2024.109554
Kehinde S Olaniyi, Stephanie E Areloegbe, Mohd Z Ul Haq Shah
Background: Besides ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) also present a number of systemic disturbances including functional derangements in the adipose tissue which possibly aggravates the endocrinometabolic abnormality in PCOS. Epigenetic changes have been implicated in metabolic-related disorders including PCOS. However, its pathogenic involvement in adipose-ovarian dysfunction is unclear. Therefore, the present research was designed to investigate the impact of epigenetic regulator, particularly short chain fatty acids (SCFAs) on adipose-ovarian dysfunction in PCOS rat model.
Materials and methods: Eight-weeks-old female Wistar rats were allotted into four groups of n = 5, namely control, sodium acetate (SACT), letrozole (LETZ), and LETZ + SACT. Letrozole (1 mg/kg; p.o.) was administered daily for 21 days to induce PCOS. Thereafter, the animals were treated daily with SACT (200 mg/kg; p.o.) for 6 weeks.
Results: Letrozole-induced PCOS rats were presented with androgen excess, insulin resistance/hyperinsulinemia, ovarian cystic follicles, increased levels of anti-Mullerian hormone, leptin, with a corresponding decrease in 17-β estradiol, and adiponectin. In addition, the LETZ group also showed dyslipidemia, decreased levels of adipose/ovarian sirtuin-1, adipose triglyceride, increased lipase activity as well as ovarian triglyceride, with corresponding increase in adipose/ovarian lipid peroxidation, caspase-6, TGF-β1, inflammatory response (TNF-α, NF-κB and MIF) and decreased GSH. Adipose/ovarian mitofusin 2 depletion was observed in LETZ group and this was accompanied by elevated HDAC2. Nevertheless, administration of acetate reversed these perturbations.
Conclusion: Overall, the present results suggest that acetate ameliorates adipose-ovarian metabolic and endocrine disruptions that accompany PCOS, and these beneficial effects of acetate are associated with reduction of HDAC2 levels and elevation of mitofusin 2/sirtuin-1.
{"title":"Acetate abates adipose-ovarian endocrinometabolic disturbance in experimentally induced polycystic ovarian syndrome.","authors":"Kehinde S Olaniyi, Stephanie E Areloegbe, Mohd Z Ul Haq Shah","doi":"10.1016/j.steroids.2024.109554","DOIUrl":"https://doi.org/10.1016/j.steroids.2024.109554","url":null,"abstract":"<p><strong>Background: </strong>Besides ovarian dysfunction and infertility, individuals with polycystic ovarian syndrome (PCOS) also present a number of systemic disturbances including functional derangements in the adipose tissue which possibly aggravates the endocrinometabolic abnormality in PCOS. Epigenetic changes have been implicated in metabolic-related disorders including PCOS. However, its pathogenic involvement in adipose-ovarian dysfunction is unclear. Therefore, the present research was designed to investigate the impact of epigenetic regulator, particularly short chain fatty acids (SCFAs) on adipose-ovarian dysfunction in PCOS rat model.</p><p><strong>Materials and methods: </strong>Eight-weeks-old female Wistar rats were allotted into four groups of n = 5, namely control, sodium acetate (SACT), letrozole (LETZ), and LETZ + SACT. Letrozole (1 mg/kg; p.o.) was administered daily for 21 days to induce PCOS. Thereafter, the animals were treated daily with SACT (200 mg/kg; p.o.) for 6 weeks.</p><p><strong>Results: </strong>Letrozole-induced PCOS rats were presented with androgen excess, insulin resistance/hyperinsulinemia, ovarian cystic follicles, increased levels of anti-Mullerian hormone, leptin, with a corresponding decrease in 17-β estradiol, and adiponectin. In addition, the LETZ group also showed dyslipidemia, decreased levels of adipose/ovarian sirtuin-1, adipose triglyceride, increased lipase activity as well as ovarian triglyceride, with corresponding increase in adipose/ovarian lipid peroxidation, caspase-6, TGF-β1, inflammatory response (TNF-α, NF-κB and MIF) and decreased GSH. Adipose/ovarian mitofusin 2 depletion was observed in LETZ group and this was accompanied by elevated HDAC2. Nevertheless, administration of acetate reversed these perturbations.</p><p><strong>Conclusion: </strong>Overall, the present results suggest that acetate ameliorates adipose-ovarian metabolic and endocrine disruptions that accompany PCOS, and these beneficial effects of acetate are associated with reduction of HDAC2 levels and elevation of mitofusin 2/sirtuin-1.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"109554"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872839","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 : 2024-12-09DOI: 10.1016/j.steroids.2024.109551
Fraydoon Rastinejad
Nuclear receptors (NRs) regulate gene expression in response to hormonal signals, influencing diverse physiological processes and diseases. Structural and dynamics investigations based on X-ray crystallography, cryo-electron microscopy (cryo-EM), hydrogen-deuterium exchange mass spectrometry, and molecular dynamics simulations, have significantly deepened our understanding of the conformational states, dynamics, and interdomain interactions of multi-domain NRs. Structural studies have examined heterodimeric complexes such as peroxisome proliferator-activated receptor gamma (PPAR-γ) with retinoid X receptor alpha (RXRα), liver X receptor beta (LXRβ) with RXRα, and retinoic acid receptor beta (RARβ) with RXRα, as well as homodimers like hepatic nuclear factor 4 alpha (HNF-4α), androgen receptor (AR), and glucocorticoid receptor (GR). These investigations highlight critical allosteric communication between ligand-binding domains (LBDs) and DNA-binding domains (DBDs), emphasizing the roles of flexible hinge regions and N-terminal segments in adapting to diverse DNA configurations. Both non-steroid receptor heterodimers and homodimers exhibit robust interdomain connections that mediate allosteric signaling. For instance, AR demonstrates three distinct conformational states that underscore its dynamic behavior, while GR exhibits unique ligand-dependent domain interactions shaping receptor signaling. The collective findings so far suggest a conserved mechanism of cross-domain communication across the NR family. Supported by complementary biophysical, spectroscopic, mutagenesis, and computational studies, this body of research has elucidated the nature of domain-domain interfaces and their pivotal roles in regulating the transcriptional activity of steroid and non-steroid receptors.
{"title":"Allosteric communications between domains of nuclear receptors.","authors":"Fraydoon Rastinejad","doi":"10.1016/j.steroids.2024.109551","DOIUrl":"10.1016/j.steroids.2024.109551","url":null,"abstract":"<p><p>Nuclear receptors (NRs) regulate gene expression in response to hormonal signals, influencing diverse physiological processes and diseases. Structural and dynamics investigations based on X-ray crystallography, cryo-electron microscopy (cryo-EM), hydrogen-deuterium exchange mass spectrometry, and molecular dynamics simulations, have significantly deepened our understanding of the conformational states, dynamics, and interdomain interactions of multi-domain NRs. Structural studies have examined heterodimeric complexes such as peroxisome proliferator-activated receptor gamma (PPAR-γ) with retinoid X receptor alpha (RXRα), liver X receptor beta (LXRβ) with RXRα, and retinoic acid receptor beta (RARβ) with RXRα, as well as homodimers like hepatic nuclear factor 4 alpha (HNF-4α), androgen receptor (AR), and glucocorticoid receptor (GR). These investigations highlight critical allosteric communication between ligand-binding domains (LBDs) and DNA-binding domains (DBDs), emphasizing the roles of flexible hinge regions and N-terminal segments in adapting to diverse DNA configurations. Both non-steroid receptor heterodimers and homodimers exhibit robust interdomain connections that mediate allosteric signaling. For instance, AR demonstrates three distinct conformational states that underscore its dynamic behavior, while GR exhibits unique ligand-dependent domain interactions shaping receptor signaling. The collective findings so far suggest a conserved mechanism of cross-domain communication across the NR family. Supported by complementary biophysical, spectroscopic, mutagenesis, and computational studies, this body of research has elucidated the nature of domain-domain interfaces and their pivotal roles in regulating the transcriptional activity of steroid and non-steroid receptors.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109551"},"PeriodicalIF":2.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802309","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 : 2024-12-09DOI: 10.1016/j.steroids.2024.109553
Hyejin Moon, Hongjoon Yoon, Hana Jung, Tae Hoon Lee, Hakwon Kim
Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 and CCL22 chemokines, which serve as biomarkers for immune cell trafficking in skin inflammation. Initially, the 3-epimer of α-spinasterol, which results from inversion of stereochemistry at the C-3 position of α-spinasterol, was synthesized using the Mitsunobu reaction. Subsequently, new compounds were synthesized by introducing azido, amino, and amide groups at the C-3 position of α-spinasterol or 3-epi-α-spinasterol. The anti-inflammatory activity of these compounds was evaluated by examining their inhibitory effects on the mRNA expression of CCL17 and CCL22. Among these derivatives, 3α-8, 3α-12b, and 3α-12c exhibited potential anti-inflammatory activity in vitro, compared to α-spinasterol. Furthermore, compound 3α-8 showed even greater activity than 3α-12b and 3α-12c, underscoring its potential as a highly effective agent. These results suggest that the newly synthesized α-spinasterol derivatives hold promise as candidates for skin inflammation therapeutics.
{"title":"Synthesis of novel α-spinasterol derivatives and their inhibitory effects on CCL17 and CCL22 chemokine expression.","authors":"Hyejin Moon, Hongjoon Yoon, Hana Jung, Tae Hoon Lee, Hakwon Kim","doi":"10.1016/j.steroids.2024.109553","DOIUrl":"10.1016/j.steroids.2024.109553","url":null,"abstract":"<p><p>Natural α-spinasterol is well known for its various biological activities. In this study, we investigated the anti-inflammatory effects of newly synthesized α-spinasterol derivatives by tracking the expression of CCL17 and CCL22 chemokines, which serve as biomarkers for immune cell trafficking in skin inflammation. Initially, the 3-epimer of α-spinasterol, which results from inversion of stereochemistry at the C-3 position of α-spinasterol, was synthesized using the Mitsunobu reaction. Subsequently, new compounds were synthesized by introducing azido, amino, and amide groups at the C-3 position of α-spinasterol or 3-epi-α-spinasterol. The anti-inflammatory activity of these compounds was evaluated by examining their inhibitory effects on the mRNA expression of CCL17 and CCL22. Among these derivatives, 3α-8, 3α-12b, and 3α-12c exhibited potential anti-inflammatory activity in vitro, compared to α-spinasterol. Furthermore, compound 3α-8 showed even greater activity than 3α-12b and 3α-12c, underscoring its potential as a highly effective agent. These results suggest that the newly synthesized α-spinasterol derivatives hold promise as candidates for skin inflammation therapeutics.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109553"},"PeriodicalIF":2.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812970","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 : 2024-12-07DOI: 10.1016/j.steroids.2024.109552
Ying Deng, Ning Yang, Jun Wang, Taotao Tu
This study investigates the causal relationships between hormone levels and growth and development of children, focusing specifically on height disparities in cases of dwarfism. Besides utilizing double-debiased machine learning approach, the study integrates three alternative causal inference methods: partialing-out lasso linear regression, cross-fit partialing-out lasso linear regression, and post-double selection LASSO. These machine learning techniques are pivotal in identifying causal effects within observational data. The findings reveal a positive correlation between luteinizing hormone (LH) levels and adolescent height, while follicle-stimulating hormone (FSH) and the LH/FSH ratio show inverse correlations. The study underscores the significant role of hormone levels, particularly LH, in determining height, offering valuable insights that could guide future interventions or treatments for children and adolescents with dwarfism.
{"title":"Understanding the role of hormones in pediatric growth: Insights from a double-debiased machine learning approach.","authors":"Ying Deng, Ning Yang, Jun Wang, Taotao Tu","doi":"10.1016/j.steroids.2024.109552","DOIUrl":"10.1016/j.steroids.2024.109552","url":null,"abstract":"<p><p>This study investigates the causal relationships between hormone levels and growth and development of children, focusing specifically on height disparities in cases of dwarfism. Besides utilizing double-debiased machine learning approach, the study integrates three alternative causal inference methods: partialing-out lasso linear regression, cross-fit partialing-out lasso linear regression, and post-double selection LASSO. These machine learning techniques are pivotal in identifying causal effects within observational data. The findings reveal a positive correlation between luteinizing hormone (LH) levels and adolescent height, while follicle-stimulating hormone (FSH) and the LH/FSH ratio show inverse correlations. The study underscores the significant role of hormone levels, particularly LH, in determining height, offering valuable insights that could guide future interventions or treatments for children and adolescents with dwarfism.</p>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":" ","pages":"109552"},"PeriodicalIF":2.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802310","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}