Steroids最新文献

{"title":"Chronic treatment with nandrolone decanoate reduces left ventricular contractile response even when combined with strength training","authors":"Lucas D. Ferreira,&nbsp;Bruno A. Aguilar,&nbsp;João V.M. Bernal,&nbsp;Kelly Y. Melo,&nbsp;Maria E. Gerolim,&nbsp;Tallys E.V. Paixão,&nbsp;Danielle A. Tiburcio,&nbsp;Hugo C.D. Souza","doi":"10.1016/j.steroids.2024.109556","DOIUrl":"10.1016/j.steroids.2024.109556","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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 (<em>T</em>-VEH and <em>T</em>-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.</div></div><div><h3>Results</h3><div>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 <em>T</em>-VEH). The NAN group exhibited reductions in coronary perfusion pressure, LVP, and maximum and minimum dP/dT compared to the VEH and <em>T</em>-VEH groups, while the <em>T</em>-NAN group showed reduced values for coronary perfusion pressure and LVP compared to the VEH group.</div></div><div><h3>Conclusions</h3><div>Nandrolone decanoate treatment at supraphysiological doses reduced left ventricular performance. In turn, strength training appeared to provide minimal attenuation of these impairments.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109556"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","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}

{"title":"Understanding the role of hormones in pediatric growth: Insights from a double-debiased machine learning approach","authors":"Ying Deng ,&nbsp;Ning Yang ,&nbsp;Jun Wang ,&nbsp;Taotao Tu","doi":"10.1016/j.steroids.2024.109552","DOIUrl":"10.1016/j.steroids.2024.109552","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109552"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","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}

{"title":"Structural and functional characterization of genes and enzymes involved in withanolide biosynthesis in Physalis alkekengi L.","authors":"Swati Gupta ,&nbsp;Bashir Akhlaq Akhoon ,&nbsp;Deepak Sharma ,&nbsp;Deepika Singh ,&nbsp;Sanjana Kaul ,&nbsp;Manoj Kumar Dhar","doi":"10.1016/j.steroids.2024.109557","DOIUrl":"10.1016/j.steroids.2024.109557","url":null,"abstract":"<div><div><em>Physalis alkekengi</em> 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 (<em>PaFPPS, PaSQS, PaSQE, PaCAS, PaHYD1, and PaDWF5-1</em>) involved in the biosynthesis of withanolides, marking the first characterization of these genes in <em>P. alkekengi</em>. Our findings revealed highly conserved amino acid sequences in <em>P. alkekengi</em>, with maximum similarity observed with <em>Withania somnifera</em>. Notably, essential domains crucial for enzyme function were preserved in <em>P. alkekengi</em>, 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 <em>P. alkekengi</em> 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 <em>P. alkekengi</em>, with maximum production observed in leaves and flowers. These findings suggest that <em>P. alkekengi</em> holds promise as an alternative to <em>W. somnifera</em> for large-scale industrial production of withanolides, particularly withanolide A. Using <em>P. alkekengi</em> eliminates the need to sacrifice the plant, which is typically required in traditional extraction methods from the roots of <em>W. somnifera.</em></div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109557"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","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}

{"title":"Acetate abates adipose-ovarian endocrinometabolic disturbance in experimentally induced polycystic ovarian syndrome","authors":"Kehinde S. Olaniyi ,&nbsp;Stephanie E. Areloegbe ,&nbsp;Mohd Z. ul haq Shah","doi":"10.1016/j.steroids.2024.109554","DOIUrl":"10.1016/j.steroids.2024.109554","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Materials and Methods</h3><div>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; <em>p.o.</em>) was administered daily for 21 days to induce PCOS. Thereafter, the animals were treated daily with SACT (200 mg/kg; <em>p.o.</em>) for 6 weeks.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109554"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","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}

{"title":"Pancreastatin inhibitor PSTi8 improves ovarian health in Letrozole-HFD induced PCOS rats by ameliorating metabolic and reproductive parameters","authors":"Shubhi Yadav ,&nbsp;Shailesh Dadge ,&nbsp;Richa Garg ,&nbsp;Umesh K. Goand ,&nbsp;Arun Agarwal ,&nbsp;Divya Chauhan ,&nbsp;Jiaur R. Gayen","doi":"10.1016/j.steroids.2024.109558","DOIUrl":"10.1016/j.steroids.2024.109558","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109558"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","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}

{"title":"PTX3 impairs granulosa cell function by promoting the secretion of inflammatory cytokines in M1 macrophages via the JAK pathway","authors":"Ying Chen ,&nbsp;Xiaofang Luo ,&nbsp;Yizhe Li ,&nbsp;Linhong Liu ,&nbsp;Zhen Liu ,&nbsp;Yunyue Tan ,&nbsp;Ying Chen","doi":"10.1016/j.steroids.2024.109541","DOIUrl":"10.1016/j.steroids.2024.109541","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is an endocrine disorder syndrome among women in their reproductive years and is often linked to chronic inflammation. Pentraxin 3 (PTX3), a member of the pentraxin protein family, plays a key role in inflammation. In our study, we explored whether PTX3 influences granulosa cell function via its involvement in inflammation. Our analysis revealed elevated PTX3 concentrations in the follicular fluid and granulosa cells of patients with PCOS. Overexpression of PTX3 promoted apoptosis in the cultured murine granulosa cell line KK1 and inhibited the proliferation of these cells. Additionally, it suppressed the expression of luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR), as well as those of key enzymes involved in steroid hormone synthesis, CYP19A1, and HSD3β, leading to reduced secretion of estradiol and progesterone. Moreover, both recombinant PTX3 protein and PTX3 secreted by granulosa cells (GCs) promoted the secretion of inflammatory cytokines IL-1β, IL-6, and TNF-α by M1 macrophages via the JAK pathway, which impaired the function of granulosa cells. This study may advance the understanding of cell–cell interactions in follicles and the inflammatory factors that contribute to PCOS pathophysiology.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"214 ","pages":"Article 109541"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692937","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}

{"title":"Cardioprotective effects of S-equol, a soybean metabolite with estrogen activity, and role of the PI3K/Akt pathway in a male rat model of ischemic reperfusion","authors":"Mariko Yamada ,&nbsp;Yosuke Nakadate ,&nbsp;Keisuke Omiya ,&nbsp;Takeshi Oguchi ,&nbsp;Masako Abe ,&nbsp;Takashi Matsukawa","doi":"10.1016/j.steroids.2024.109542","DOIUrl":"10.1016/j.steroids.2024.109542","url":null,"abstract":"<div><h3>Purpose</h3><div>S-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardioprotective effects against ischemia–reperfusion injury, whether S-equol shares this capability remains uncertain. This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium using an isolated rat heart model and investigate the involvement of PI3K/Akt signaling pathway.</div></div><div><h3>Methods</h3><div>Male rat hearts were perfused using the Langendorff system and divided into four groups: 1) modified Krebs–Henseleit (KH) buffer containing 1 μmol/L S-equol (EQ); 2) KH buffer (Cont); 3) KH buffer supplemented with 1 μmol/L S-equol and 100 nmol/L wortmannin (a specific PI3K inhibitor) (EQW); or 4) KH buffer containing wortmannin (ContW). After stabilization, each group was perfused for 20 min before undergoing 7.5 min of no-flow ischemia, followed by 20 min reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (left ventricle [LV] dP/dt max)<!--> <!-->after 20 min of reperfusion. Myocardial Akt and glycogen synthase kinase-3 beta (GSK-3β) were assayed using western blotting.</div></div><div><h3>Results</h3><div>LV dP/dt max was greater in the EQ group than that in the Cont group after 15 and 20 min of reperfusion; however, this effect was attenuated in the presence of PI3K inhibitors. S-equol treatment increased Akt and suppressed GSK-3β expression in the EQ group compared to that in the Cont group. However, these effects were not observed in the presence of wortmannin.</div></div><div><h3>Conclusion</h3><div>S-equol exerts a protective effect against myocardial ischemia–reperfusion injury, possibly by activating PI3K/Akt signaling.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"213 ","pages":"Article 109542"},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743700","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}

{"title":"Comparison of a chemiluminescence immunoassay with LC–MS/MS in the determination of the plasma aldosterone concentration in patients with impaired renal function","authors":"Qiurong Zeng ,&nbsp;Junlong Li ,&nbsp;Yi Yang,&nbsp;Yifan He,&nbsp;Ying Song,&nbsp;Jinbo Hu,&nbsp;Yue Wang,&nbsp;Qifu Li,&nbsp;Shumin Yang,&nbsp;on behalf of the Chongqing Primary Aldosteronism Study CONPASS Group","doi":"10.1016/j.steroids.2024.109540","DOIUrl":"10.1016/j.steroids.2024.109540","url":null,"abstract":"<div><h3>Purpose</h3><div>Compared with chemiluminescence immunoassay (CLIA), the quantification of the plasma aldosterone concentration (PAC) via liquid chromatography–tandem mass spectrometry (LC–MS/MS) yields lower values. The extent to which this difference is exacerbated by a reduced glomerular filtration rate (eGFR) is unclear. Therefore, this study aims to assess the impact of renal insufficiency on PAC as measured by CLIA using LC–MS/MS as the reference method.</div></div><div><h3>Methods</h3><div>In subjects with a normal or reduced estimated eGFR, the PAC was measured using both LC–MS/MS and two different CLIA kits (Mindray and Liaison).</div></div><div><h3>Results</h3><div>In total, 383 patients were included in our study. Among them, 71 subjects had eGFRs &gt; 90 (Group one), 79 had eGFRs range from 60 to 89 (Group two), 108 had eGFR range from 30 to 59 (Group three), 51 had eGFRs range from 15 to 29 (Group four), and 74 had eGFRs &lt; 15 (Group five) ml/min per 1.73 m². In all the subjects, PAC as measured by CLIA [68.2 (37.1–122.1) pg/ml for Mindray, 109.0 (68.1–170.0) pg/ml for Liaison] were significantly higher than those measured by LC–MS/MS [47.2 (22.9–88.7) pg/ml]. PAC as measured by CLIA was positively correlated with PAC as measured by LC–MS/MS, but the correlation coefficient gradually decreased as eGFR decreased. Between the LC–MS/MS and Liaison CLIA kits, the difference in PAC values increased with reduced eGFR in groups one through five (76.8 %, 69.2 %, 113.2 %, 152.2 %, and 476.2 % for groups one through five, respectively). However, this difference increased only in Group five with the Mindray CLIA kit (46.4 %, 48.1 %, 45.7 %, 45.0 %, and 74.9 % for groups one through five, respectively).</div></div><div><h3>Conclusion</h3><div>CLIA progressively overestimated PAC as eGFR decreased, particularly with the Liaison method, indicating the need for caution when interpreting these measurements in patients with impaired renal function. In patients with impaired renal function, LC‒MS/MS measurements for PAC are preferable.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"213 ","pages":"Article 109540"},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689009","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}

{"title":"Unraveling the impact of semaglutide in a diabetic rat model of testicular dysfunction: Insights into spermatogenesis pathways and miRNA-148a-5p","authors":"Basel A. Abdel-Wahab ,&nbsp;Ehab A.M. El-Shoura ,&nbsp;Mohammed S. Habeeb ,&nbsp;Nayef A. Aldabaan ,&nbsp;Yasmine H. Ahmed ,&nbsp;Dalia Zaafar","doi":"10.1016/j.steroids.2024.109537","DOIUrl":"10.1016/j.steroids.2024.109537","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes has been a long-known risk factor for male sexual dysfunction, which may be caused by persistent hyperglycemia, oxidative stress, and spermatogenesis inhibition. This study explored the potential of Semaglutide (Sem) to alleviate testicular dysfunction and spermatogenesis impairment in diabetic rats to understand the molecular mechanism of this protective effect.</div></div><div><h3>Methodology</h3><div>A controlled experiment was conducted where 28 adult male rats were divided into four groups: control, Semaglutide, diabetic, and diabetes + Sem. Diabetes was induced using a single STZ dose (50 mg/kg, i.p.). At the same time, Sem was administered as a daily subcutaneous dose (25 nmol/kg) for four weeks after the confirmed diagnosis of diabetes.</div><div>Several biochemical and histochemical analyses were performed in addition to mating behavior assessments. The estimation of spermatogenesis-related genes and proteins was conducted using PCR and western blotting techniques.</div></div><div><h3>Results</h3><div>revealed promising outcomes, wherein Sem treatment effectively mitigated diabetes-induced sexual and testicular dysfunction. Specifically, it regulated the disrupted redox balance, restored spermatogenesis gene and protein levels, modulated hormonal profiles, and mitigated testicular inflammation.</div></div><div><h3>Conclusion</h3><div>Sem protects against diabetes-induced testicular and sexual impairments by influencing several pathways and restoring spermatogenesis-related genes and proteins. Future studies may involve a potential investigation of Sem translational applications in clinical settings for treating male infertility associated with diabetes.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"213 ","pages":"Article 109537"},"PeriodicalIF":2.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649180","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}

{"title":"Ascorbic acid Mitigates behavioural disturbances associated with letrozole-induced PCOS via switching-off JAK2/STAT5 and JAK2/ERK1/2 pathways in rat hippocampus","authors":"Muhammed A. Saad ,&nbsp;Alyasaa A. Rastanawi ,&nbsp;Ayman E. El-Sahar ,&nbsp;Alshaymaa A. Z. El-Bahy","doi":"10.1016/j.steroids.2024.109528","DOIUrl":"10.1016/j.steroids.2024.109528","url":null,"abstract":"<div><h3>Purpose</h3><div>Polycystic ovary syndrome (PCOS) is an endocrine disorder with the highest prevalence among other disorders in sexually-active women. It is associated with broad-spectrum hormonal and metabolic disturbances with behavioural difficulties. Experimentally, letrozole administration causes similar findings. Ascorbic acid is powerful anti-oxidant; and its cellular levels decrease with “hyperglycemic and poor anti-oxidative” status, which is, a main hallmark of PCOS. Thus, ascorbic acid administration may prevent the induction of PCOS and its consequences.</div><div><strong>Basic procedures:</strong> Forty female rats were divided into four groups (n = 10 in each): normal control (CTRL), ascorbic acid (ASC), letrozole (LTZ), and ascorbic acid + letrozole (ASC + LTZ) group. Behavioural tests (Y-maze spontaneous alteration, tail suspension test, forced swimming test) were performed. In serum, hormones (testosterone, estradiol, progesterone), glycemia (blood glucose, insulin and HOMA-IR) and oxidative stress (SOD activity, GSH) markers were measured. In hippocampus, inflammation and apoptosis indicators (p-JAK2, p-STAT5, p-ERK1/2, NF-κB, BAX, Bcl2, BAX/Bcl2 ratio) and neurotransmitters (DA, 5-HT, NE, BDNF) were determined. Lastly, ovary histopathological investigation was conducted to confirm PCOS induction.</div><div><strong>Principal results:</strong> Letrozole induced PCOS with subsequent disturbances. Testosterone levels were augmented while estradiol and progesterone were declined. Fasting blood glucose, insulin, HOMA-IR and oxidative stress markers were elevated. The expression of p-JAK2, p-STAT5, p-ERK1/2, BAX and the levels of NF-κB were increased, but Bcl2 expression, monoamines and BDNF levels were lowered. Importantly, ASC restored the last mentioned parameters markedly. <strong>Major conclusions:</strong> Ascorbic acid mitigated the behavioural difficulties of PCOS possibly by switching-off JAK2/STAT5 and JAK2/ERK1/2 pathways in hippocampus along with its neurotransmission-improving, hormonal-normalizing, anti-hyperglycemic and anti-oxidative effects.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"213 ","pages":"Article 109528"},"PeriodicalIF":2.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628494","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}