Steroids[JOURNAL]
Sun
200 papers
Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis.
Yadav A, Verma A, Singh SK … +4 more , Prakash R, Srivastava S, Sethi A, Pratap Singh R
Steroids · 2024 Dec · PMID 39307446 · Publisher ↗
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...
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.
Investigating the influence of estrous cycle-dependent hormonal changes on neurogenesis in adult mice.
Mirzaeian L, Bahrehbar K, Emamdoust M … +3 more , Amiri M, Azari M, Taghi Ghorbanian M
Steroids · 2024 Dec · PMID 39305945 · Publisher ↗
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 evaluat...
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.
Neurotoxic mechanisms of dexamethasone in SH-SY5Y neuroblastoma cells: Insights into bioenergetics, oxidative stress, and apoptosis.
Elmorsy EM, Al-Ghafari AB, Al Doghaither HA … +2 more , Fawzy MS, Shehata SA
Steroids · 2024 Dec · PMID 39303897 · Publisher ↗
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 inadequ...
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.
Ergostanes from the mushroom Trametes versicolor and their cancer cell inhibition: In vitro and in silico evaluation.
Njue AW, Omolo J, Ramos RS … +2 more , Santos CBR, Kimani NM
Steroids · 2024 Dec · PMID 39303896 · Publisher ↗
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,5...
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.
A review of metabolic and microbial influences on women with polycystic ovarian syndrome.
Ravat FK, Goswami JR, Nair SM … +1 more , Thummar KN
Steroids · 2024 Dec · PMID 39278517 · Publisher ↗
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 o...
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.
Structural perspectives on the androgen receptor, the elusive shape-shifter.
Johnson MJ, Wasmuth EV
Steroids · 2024 Nov · PMID 39208923 · Full text
The androgen receptor (AR) is a type I nuclear receptor and master transcription factor responsible for development and maintenance of male secondary sex characteristics. Aberrant AR activity is associated with numerous...
The androgen receptor (AR) is a type I nuclear receptor and master transcription factor responsible for development and maintenance of male secondary sex characteristics. Aberrant AR activity is associated with numerous diseases, including prostate cancer, androgen insensitivity syndrome, spinal and bulbar muscular atrophy, and androgenic alopecia. Recent studies have shown that AR adopts numerous conformations that can modulate its ability to bind and transcribe its target DNA substrates, a feature that can be hijacked in the context of cancer. Here, we summarize a series of structural observations describing how this elusive shape-shifter binds to multiple partners, including self-interactions, DNA, and steroid and non-steroidal ligands. We present evidence that AR's pervasive structural plasticity confers an ability to broadly bind and transcribe numerous ligands in the normal and disease state, and explain the structural basis for adaptive resistance mutations to antiandrogen treatment. These evolutionary features are integral to receptor function, and are commonly lost in androgen insensitivity syndrome, or reinforced in cancer.
Nandrolone decanoate induced kidney injury through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB pathway: The effect of moderate exercise.
Shirpoor A, Naderi R
Steroids · 2024 Nov · PMID 39208922 · Publisher ↗
Anabolic-androgenic steroids (AAS) abuse is linked to some abnormalities in several tissues including the kidney. However, the precise molecular mediators involved in AAS-induced kidney disorder remain elusive. The main...
Anabolic-androgenic steroids (AAS) abuse is linked to some abnormalities in several tissues including the kidney. However, the precise molecular mediators involved in AAS-induced kidney disorder remain elusive. The main objective of the present study was to investigate the effect of Nandrolone decanoate on kidney injury alone or in combination with moderate exercise and its related mechanisms. Thirty-two male Wistar rats were subdivided randomly into four groups. control (Con), Nandrolone (10 mg/kg)(N), Exercise (Exe), Nandrolone + Exercise (N+Exe). RESULTS: After 6 weeks, nandrolone treatment led to a significant increase in functional parameters such as serum cystatin c, urea, creatinine, albuminuria and Albumin/ creatinine ratio indicating kidney dysfunction. Moreover, nandrolone treatment increased vacuolization, focal inflammation, hemorragia, cast formation fibrosis in the renal tissue of rats. miRNA-146a increased in kidney tissue after nandrolone exposure by using RT-PCR which may be considered idealtheranomiRNAcandidates for diagnosis and treatment. Western blotting indicated that IRAK1, TRAF6, TNF-α, NF-κB, iNOS and TGF-β protein expressions were considerably elevated in the kidneys of nandrolone treated rats. Moderate exercise could alleviate the renal dysfunction, histological abnormalities and aforementioned proteins. Our findings suggested that nandrolone consumption can cause damage to kidney tissue probably through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB and TGF-β pathway. These results provide future lines of research in the identification of theranoMiRNAs related to nandrolone treatment, which can be ameliorated by moderate exercise.
The interpretation of immunometric, chromatographic and mass spectrometric data for steroids in diagnosis of endocrine disorders.
Honour JW
Steroids · 2024 Nov · PMID 39214232 · Publisher ↗
The analysis of steroids for endocrine disorders is in transition from immunoassay of individual steroids to more specific chromatographic and mass spectrometric methods with simultaneous determination of several steroid...
The analysis of steroids for endocrine disorders is in transition from immunoassay of individual steroids to more specific chromatographic and mass spectrometric methods with simultaneous determination of several steroids. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) offer unrivalled analytical capability for steroid analysis. These specialist techniques were often judged to be valuable only in a research laboratory but this is no longer the case. In a urinary steroid profile up to 30 steroids are identified with concentrations and excretion rates reported in a number of ways. The assays must accommodate the wide range in steroid concentrations in biological fluids from micromolar for dehydroepiandrosterone sulphate (DHEAS) to picomolar for oestradiol and aldosterone. For plasma concentrations, panels of 5-20 steroids are reported. The profile results are complex and interpretation is a real challenge in order to inform clinicians of likely implications. Although artificial intelligence and machine learning will in time generate reports from the analysis this is a way off being adopted into clinical practice. This review offers guidance on current interpretation of the data from steroid determinations in clinical practice. Using this approach more laboratories can use the techniques to answer clinical questions and offer broader interpretation of the results so that the clinician can understand the conclusion for the steroid defect, and can be advised to program further tests if necessary and instigate treatment. The biochemistry is part of the patient workup and a clinician led multidisciplinary team discussion of the results will be required for challenging patients. The laboratory will have to consider cost implications, bearing in mind that staff costs are the highest component. GC-MS and LC-MS/MS analysis of steroids are the choices. Steroid profiling has enormous potential to improve diagnosis of adrenal disorders and should be adopted in more laboratories in favour of the cheap, non-specific immunological methods.
Exploring the impact of estrogen-related receptor gamma on metabolism and disease.
Sadasivam N, Park WR, Choi B … +3 more , Seok Jung Y, Choi HS, Kim DK
Steroids · 2024 Nov · PMID 39159854 · Publisher ↗
Estrogen-related receptor gamma (ERRγ) is a member of the ERR orphan nuclear receptor family which possesses three subtypes, α, β, and γ. ERRγ is reportedly predominantly expressed in metabolically active tissues and cel...
Estrogen-related receptor gamma (ERRγ) is a member of the ERR orphan nuclear receptor family which possesses three subtypes, α, β, and γ. ERRγ is reportedly predominantly expressed in metabolically active tissues and cells, which promotes positive and negative effects in different tissues. ERRγ overexpression in the liver, pancreas, and thyroid cells is related to liver cancer, oxidative stress, reactive oxygen species (ROS) regulation, and carcinoma. Reduced ERRγ expression in the brain, immune cells, tumor cells, and energy metabolism causes neurological dysfunction, gastric cancer, and obesity. ERRγ is a constitutive receptor; however, its transcriptional activity also depends on co-regulators, agonists, and antagonists, which, when after forming a complex, can play a role in targeting and treating diseases. Moreover, ERRγ has proven crucial in regulating cellular and metabolic activity. However, many functions mediated via ERRγ remain unknown and require further exploration. Hence, considering the importance of ERRγ, this review focuses on the critical findings and interactions between ERRγ and co-regulators, agonists, and antagonists alongside its relationship with downstream and upstream signaling pathways and diseases. This review highlights new findings and provides a path to understanding the current ideas and future studies on ERRγ-mediated cellular activity.
Recent advances in the synthesis of cholesterol-based triazoles and their biological applications.
Bendi A, Vashisth C, Yadav S … +2 more , Pundeer R, Raghav N
Steroids · 2024 Nov · PMID 39155033 · Publisher ↗
Double-headed warheads focusing on the pharmacological aspects as well as membrane permeability can contribute a lot to medicinal chemistry. Over the past few decades, a lot of research has been conducted on steroid-hete...
Double-headed warheads focusing on the pharmacological aspects as well as membrane permeability can contribute a lot to medicinal chemistry. Over the past few decades, a lot of research has been conducted on steroid-heterocycle conjugates as possible therapeutic agents against a variety of disorders. In the second half of the 20th century, successful research was conducted on cholesterol-based heterocyclic moieties. Keeping in view the biological significance of various triazoles, research on fusion with cholesterol has emerged. This review has been designed to explore the chemistry of cholesterol-based triazoles for the duration from 2010 to 2023 and their significance in medicinal chemistry.
1α,25-hydroxyvitamin D/VDR suppresses stem-like properties of ovarian cancer cells by restraining nuclear translocation of β-catenin.
Li J, Hou Y, Ding H … +2 more , Wang P, Li B
Steroids · 2024 Nov · PMID 39151767 · Publisher ↗
Several studies have indicated that 1α,25-hydroxyvitamin D [1α,25(OH)D] inhibits the proliferation and metastasis of cancer cells through suppressing epithelial-mesenchymal transition. However, its influence on the trans...
Several studies have indicated that 1α,25-hydroxyvitamin D [1α,25(OH)D] inhibits the proliferation and metastasis of cancer cells through suppressing epithelial-mesenchymal transition. However, its influence on the translocation of β-catenin remains unclear. In the present study, ovarian cancer stem-like cells (CSCs), including side population (SP) and CD44/CD117, were isolated from mouse ovarian surface epithelial (MOSE) cells with malignant transformation. The findings revealed that 1α,25(OH)D obviously reduced the sphere-forming ability, as well as Notch1 and Klf levels. Moreover, the limiting dilution assay demonstrated that 1α,25(OH)D effectively hindered the tumorigenesis of ovarian CSCs in vitro. Notably, treatment with 1α,25(OH)D led to a substantial increase in the cell population of CD44/CD117 forming one tumor from ≤ 100 to 445 in orthotopic transplanted model, indicating a pronounced suppression of stemness of ovarian CSCs. Additionally, 1α,25(OH)D robustly promoted the translocation of β-catenin from the nuclear to the cytoplasm through directly binding to VDR, which resulted in decreased levels of c-Myc and CyclinD1 within late MOSE cells. Taken together, these results strongly supported the role of 1α,25(OH)D in inhibiting stem-like properties in ovarian cancer cells by restraining nuclear translocation of β-catenin, thereby offering a promising target for cancer therapeutics.
Dehydroepiandrosterone supplementation improves diminished ovarian reserve clinical and in silico studies.
Moslem Ahmad H, Aldahham BJM, Yakdhan Saleh M
Steroids · 2024 Nov · PMID 39147007 · Publisher ↗
The therapeutic role of dehydroepiandrosterone (DHEA) supplementation among infertile women with diminished ovarian reserve (DOR) is still unclear. Objective evaluation of different ovarian reserve tests (ORTs) such as s...
The therapeutic role of dehydroepiandrosterone (DHEA) supplementation among infertile women with diminished ovarian reserve (DOR) is still unclear. Objective evaluation of different ovarian reserve tests (ORTs) such as serum anti-Mullerian hormone (AMH), serum follicle stimulating hormone (FSH), and antral follicle count (AFC) in women with diminished ovarian reserve is required. This is a cross-sectional study performed in Mosul city, Iraq, with 122 infertile women who had been diagnosed with DOR. The enrolled women's age ranged from 18 to 45 years old (mean age of 29.46 ± 2.64 years). The ages of the enrolled women ranged from 18 to 45 years (mean age of 29.46 ± 2.64 years). To assess the influence of DHEA supplements (25 mg, three times/day for 12 weeks) across different age groups, the women were initially divided into three groups (18 to 27 years old, 28 to 37 years old, and ≥ 38 years old). Significant differences were noticed in AMH, FSH, level and AFC before and after DHEA supplementation. (AMH: 0.64 ± 0.82 vs. 1.98 ± 1.32, AFC: 2.86 ± 0.64 vs. 5.82 ± 2.42, and FSH: 12.44 ± 3.85 vs. 8.12 ± 4.64), statistically obvious significant differences regarding the results of AMH (p < 0.001), AFC (p < 0.001), and FSH (p < 0.001). DHEA supplementations improved the ovarian reserve of the enrolled women, which was more evident in younger women (<38 years old) than older women (≥38 years old). The AMH serum levels and AFC value can be considered the best, most reliable and significant OR parameters. However, large randomized multicenter studies are required to confirm the available results and data.
Quantitative determination of plasma cholesteryl ester levels in Japanese preadolescents from the Hokkaido study using liquid chromatography/tandem mass spectrometry.
Gowda D, Gowda SGB, Ikeda A … +5 more , Ketema RM, Ait Bamai Y, Kishi R, Chiba H, Hui SP
Steroids · 2024 Nov · PMID 39147006 · Publisher ↗
Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in...
Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/μL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/μL in boys and 824 and 875 pmol/μL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity.
Rodent models in polycystic ovarian syndrome: Dissecting reproductive and metabolic phenotypes for therapeutic advancements.
Basak S, Kumar Dixit A, Kumar Dey R … +5 more , Roy S, Singh R, Nair PG, Kumar S, Babu G
Steroids · 2024 Nov · PMID 39117289 · Publisher ↗
The most prevalent reason for female infertility is polycystic ovarian syndrome (PCOS) exhibiting two of three phenotypes including biochemical or clinical hyperandrogenism, anovulation and polycystic ovaries. Insulin re...
The most prevalent reason for female infertility is polycystic ovarian syndrome (PCOS) exhibiting two of three phenotypes including biochemical or clinical hyperandrogenism, anovulation and polycystic ovaries. Insulin resistance and obesity are common in PCOS-afflicted women. Androgens are thought to be the primary cause of PCOS causing symptoms including anovulation, follicles that resemble cysts, higher levels of the luteinizing hormone (LH), increased adiposity, and insulin resistance. However, due to the heterogeneity of PCOS, it is challenging to establish a single model that accurately mimics all the reproductive and metabolic phenotypes seen in PCOS patients. In this review, we aimed to investigate rodent models of PCOS and related phenotypes with or without direct hormonal treatments and to determine the underlying mechanisms to comprehend PCOS better. We summarized rodent models of PCOS that includes direct and indirect hormone intervention and discussed the aetiology of PCOS and related phenotypes produced in rodent models. We presented combined insights on multiple rodent models of PCOS and compared their reproductive and/or metabolic phenotypes. Our review indicates that there are various models for studying PCOS and one should select a model most suitable for their purpose. This review will be helpful for consideration of rodent models for PCOS which are not conventionally used to determine mechanisms at the molecular/cellular levels encouraging development of novel treatments and control methods for PCOS.
Advances in the understanding of androgen receptor structure and function and in the development of next-generation AR-targeted therapeutics.
Effah W, Khalil M, Hwang DJ … +2 more , Miller DD, Narayanan R
Steroids · 2024 Oct · PMID 39111362 · Full text
Androgen receptor (AR) and its ligand androgens are important for development and physiology of various tissues. AR and its ligands also play critical role in the development of various diseases, making it a valuable the...
Androgen receptor (AR) and its ligand androgens are important for development and physiology of various tissues. AR and its ligands also play critical role in the development of various diseases, making it a valuable therapeutic target. AR ligands, both agonists and antagonists, are being widely used to treat pathological conditions, including prostate cancer and hypogonadism. Despite AR being studied widely over the last five decades, the last decade has seen striking advances in the knowledge on AR and discoveries that have the potential to translate to the clinic. This review provides an overview of the advances in AR biology, AR molecular mechanisms of action, and next generation molecules that are currently in development. Several of the areas described in the review are just unraveling and the next decade will bring more clarity on these developments that will put AR at the forefront of both basic biology and drug development.
Shatavarin-IV, a steroidal saponin from Asparagus racemosus, inhibits cell cycle progression and epithelial-to-mesenchymal transition in AGS cells under hyperglycemic conditions.
Chatterjee A, Roy T, Kumar Mishra V … +1 more , Swarnakar S
Steroids · 2024 Oct · PMID 39106908 · Publisher ↗
Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be u...
Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be used as therapeutics as they have greater effectiveness, reduced toxicity, and a reduced likelihood of developing multi-drug resistance in cancer treatments. The present study intended to assess the therapeutic efficacy of Shatavarin-IV - a major steroidal saponin from the roots of Asparagus racemosus, in human gastric adenocarcinoma cell line under hyperglycemic conditions and explore its mechanism of action in controlling GC progression. For the present study, AGS cells were incubated in high glucose-containing media and the effects of Shatavarin-IV therein have been evaluated. Cell proliferation, confocal microscopic imaging, flow-cytometric analysis for cell cycle and apoptosis, immunoblotting, zymography, reverse zymography, wound-healing, colony formation, and invasion assays were performed. Shatavarin-IV has a prominent effect on AGS cell proliferation; with IC50 of 2.463 µ M under hyperglycemic conditions. Shatavarin-IV induces cell cycle arrest at the G0/G1 phase, thereby preventing hyperglycemia-induced excessive cell proliferation that later on leads to apoptotic cell death at 36 h of incubation. Shatavarin-IV further inhibits the migratory and invasive potential of AGS cells by altering the expression patterns of different EMT markers. It also inhibits MMP-9 while promoting TIMP-1 activity and expression; thereby regulating ECM turnover. This is the first report demonstrating the therapeutic efficacy of Shatavarin-IV against AGS cells grown in hyperglycemic conditions, implicating new insights into the treatment paradigm of patients with GC-diabetes co-morbidity.
Corrigendum to "Effects of neural-derived estradiol on actin polymerization and synaptic plasticity-related proteins in prefrontal and hippocampal cells of mice" [Steroids 177 (2022) 108935].
Feng Y, Shi R, Hu J … +1 more , Lou S
Steroids · 2024 Oct · PMID 39068049 · Publisher ↗
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Steroidal 21-imidazolium salt derivatives: Synthesis and anticancer activity.
Sucman NS, Ya Bilan D, Cojocari SV … +13 more , Pogrebnoi VS, Stîngaci EP, Khripach VA, Zhabinskii VN, Tsybruk TV, Grabovec IP, Panibrat OV, Persoons L, Schols D, Froeyen M, Shova S, De Jonghe S, Macaev FZ
Steroids · 2024 Oct · PMID 39067611 · Publisher ↗
Nitrogen-containing steroids are known as prostate cancer therapeutics. In this work, a series of pregnane derivatives bearing an imidazolium moiety were synthesized using Δ-20-ketones as starting material. An improved a...
Nitrogen-containing steroids are known as prostate cancer therapeutics. In this work, a series of pregnane derivatives bearing an imidazolium moiety were synthesized using Δ-20-ketones as starting material. An improved approach for the construction of the 20-keto-21-heterocycle-substituted fragment involved the rearrangement of 16,17-epoxides with HCl, followed by reaction of the formed α-chloroketone with 1-substituted imidazoles. Binding affinity analysis of the imidazolium steroids and their synthetic intermediates to human CYP17A1 showed only type I (substrate-like) interactions. The strongest affinity was observed for 16α,17α-epoxy-5α-pregnan-20-on-3β-ol (K = 0.66 ± 0.05 µM). The steroid derivatives have been evaluated for antitumor activity against a range of prostate cancer cells as well as against various other solid tumor and hematologic cancer cell lines. All 21-imidazolium salts were active against the hormone-dependent prostate cancer line LNCaP. The most pronounced cytotoxicity in solid tumor and hematologic cancer cell lines was observed for intermediate product, 21-chloro-5α-pregn-16-en-20-on-3β-ol. Among the imidazolium salts, the derivatives with a single bond were more cytotoxic than their unsaturated congeners.
Steroid sulfatase in mouse liver and testis: Characterization, ontogeny and localization.
Balasubramonian B, Selcer KW
Steroids · 2024 Oct · PMID 39053631 · Publisher ↗
Steroid hormones often circulate in the plasma as inactive sulfated forms, such as estrone sulfate and dehydroepiandrosterone sulfate. The enzyme steroid sulfatase (STS) converts these steroids into active forms, mainly...
Steroid hormones often circulate in the plasma as inactive sulfated forms, such as estrone sulfate and dehydroepiandrosterone sulfate. The enzyme steroid sulfatase (STS) converts these steroids into active forms, mainly estrogens, in peripheral tissues. STS is present in most tissues, but it occurs at higher levels in certain organs, notably liver and placenta. In this study, we examined the tissue distribution of STS in a prominent laboratory model, the house mouse (Mus musculus). Tissues included were heart, liver, small intestine, skeletal muscle, and gonads of both sexes. An H-estrone-sulfate conversion assay was used to measure STS activity in tissue homogenates and extracts. STS activities were high for hepatic tissue homogenates of both genders. Testicular STS levels were similar to those of liver, while STS activities of ovary, small intestine, heart, and muscle were considerably lower. The specific STS inhibitors, EMATE and STX-64 virtually eliminated STS activity in hepatic microsomes and cytosols, verifying that the observed enzyme activity was due to STS. Enzyme kinetic assays showed Km values of 8.6 µM for liver and 9.1 µM for testis, using ES as substrate. Hepatic and testicular STS activities, measured in CHAPS-extracted microsome, were low up to 5 weeks of age and were higher through 56 weeks. Western blotting, with a specific STS antibody, confirmed the presence of STS protein (65 Da) in both liver and testis. Immunofluorescence of tissue sections detected the presence of STS protein in hepatocytes, in testicular Leydig cells and in seminiferous tubules (Leydig cells and developing germ cells). These results suggest that STS may have a significant role in testicular function.
Inhibitors of the transactivation domain of androgen receptor as a therapy for prostate cancer.
Obst JK, Tien AH, Setiawan JC … +2 more , Deneault LF, Sadar MD
Steroids · 2024 Oct · PMID 39053630 · Full text
The androgen receptor (AR) is a modular transcription factor which functions as a master regulator of gene expression. AR protein is composed of three functional domains; the ligand-binding domain (LBD); DNA-binding doma...
The androgen receptor (AR) is a modular transcription factor which functions as a master regulator of gene expression. AR protein is composed of three functional domains; the ligand-binding domain (LBD); DNA-binding domain (DBD); and the intrinsically disordered N-terminal transactivation domain (TAD). AR is transactivated upon binding to the male sex hormone testosterone and other androgens. While the AR may tolerate loss of its LBD, the TAD contains activation function-1 (AF-1) that is essential for all AR transcriptional activity. AR is frequently over-expressed in most prostate cancer. Currently, androgen deprivation therapy (ADT) in the form of surgical or chemical castration remains the standard of care for patients with high risk localized disease, advanced and metastatic disease, and those patients that experience biochemical relapse following definitive primary treatment. Patients with recurrent disease that receive ADT will ultimately progress to lethal metastatic castration-resistant prostate cancer. In addition to ADT not providing a cure, it is associated with numerous adverse effects including cardiovascular disease, osteoporosis and sexual dysfunction. Recently there has been a renewed interest in investigating the possibility of using antiandrogens which competitively bind the AR-LBD without ADT for patients with hormone sensitive, non-metastatic prostate cancer. Here we describe a class of compounds termed AR transactivation domain inhibitors (ARTADI) and their mechanism of action. These compounds bind to the AR-TAD to inhibit AR transcriptional activity in the absence and presence of androgens. Thus these inhibitors may have utility in preventing prostate cancer growth in the non-castrate setting.
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