Steroids[JOURNAL]
Sun
200 papers
Donepezil enhances the testicular protective effect of metformin in diabetic rats by modulating steroidogenic signaling and Bax/Bcl-2/Caspase-3 pathway.
Akhigbe RE, Chimezie J, Odeyemi AA … +7 more , Oyesode SO, Adesogan F, Oladipo AA, Ashonibare PJ, Akhigbe TM, Ashamu EA, Olamoyegun MA
Steroids · 2026 Apr · PMID 41610929 · Publisher ↗
BACKGROUND: Type 2 diabetes mellitus (T2DM) induces testicular damage through xanthine oxidase (XO)/uric acid (UA)/caspase-3-driven oxidative stress and apoptosis. Although metformin is effective in managing diabetes, co...
BACKGROUND: Type 2 diabetes mellitus (T2DM) induces testicular damage through xanthine oxidase (XO)/uric acid (UA)/caspase-3-driven oxidative stress and apoptosis. Although metformin is effective in managing diabetes, combined therapy is more effective. Though donepezil protects against neuronal and retinal damage in diabetic rats, its role in diabetes-induced testicular damage is yet to be reported. AIM: This study investigated the protective effects of combined metformin and donepezil treatment on testicular dysfunction in a high-fat diet/streptozotocin-induced T2DM rat model. Also, the involvement of XO/UA and Bax/Bcl-2/caspase signaling was examined. METHODS: Forty-eight 8-week-old male Wistar rats were randomly assigned into six equal groups: control, diabetes (DM), DM+metformin, donepezil, DM+donepezil, and DM+metformin+donepezil groups. RESULTS: T2DM caused testicular inflammation and oxidative stress, evidenced by elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), activation of NF-κB signaling, increased oxidative markers (MDA), and reduced antioxidant enzymes. T2DM also led to testicular apoptosis (increased Bax and caspase-3 and reduced Bcl-2). More so, T2DM repressed serum testosterone, FSH, and LH, and caused morphological disorganization of the testes, including germ cell loss and Leydig cell degeneration. Treatment with metformin and donepezil, singly or in combination, significantly mitigated these adverse effects, with the combined therapy demonstrating superior efficacy. The intervention suppressed XO/uric acid signaling, oxidative stress, and inflammatory responses via downregulation of NF-κB and apoptotic cascades. These results imply that donepezil and metformin work in concert to provide a potentially effective treatment strategy for reducing testicular damage caused by diabetes through modulation of oxidative, inflammatory, and apoptotic pathways, ultimately restoring testicular structure and function.
The protective effects of luteolin and oleuropein against dexamethasone-induced hyperlipidemia.
Aziz LN, Mahmoud MO, Ibrahim IT
Steroids · 2026 Mar · PMID 41520857 · Publisher ↗
BACKGROUND: Dexamethasone-induced hyperlipidemia is a well-documented metabolic complication associated with prolonged glucocorticoid therapy. The present study aims to investigate the potential protective effects of the...
BACKGROUND: Dexamethasone-induced hyperlipidemia is a well-documented metabolic complication associated with prolonged glucocorticoid therapy. The present study aims to investigate the potential protective effects of the selected natural antioxidants luteolin and oleuropein against dexamethasone-induced hyperlipidemia. METHODOLOGY: The study was conducted on five groups of female Wistar rats, including a normal control group, a dexamethasone-induced hyperlipidemia group, and three treatment groups. The treatment groups consisted of dexamethasone-administered rats receiving luteolin or oleuropein (100 mg/kg BW) individually or in combination (luteolin + oleuropein) for a duration of one month. RESULTS: Dexamethasone induced hyperlipidemia, hepatic injury, and oxidative stress, as evidenced by increased levels of aspartate aminotransferase (AST; +154%), alanine aminotransferase (ALT; +121%), total cholesterol (TC; +75%), triglycerides (+132%), and malondialdehyde (+85%), while reducing catalase and glutathione by approximately 50.5% and 62%, respectively, compared with the control group. Treatment with either luteolin or oleuropein individually mitigated these changes (AST: -47.0% and - 46.4%; ALT: -37.2% and - 36.4%; TC: -34.8% and - 33.1%; triglycerides: -41.7% and - 40.5%; malondialdehyde: -28.4% and - 26.0%; catalase: +79.2% and + 74.8%; and glutathione: +104.8% and + 102.3%, respectively). Combined treatment provided the greatest protection, and histological examination revealed partial restoration of normal hepatic architecture. CONCLUSION: The study suggests that luteolin and oleuropein help counteract dexamethasone-induced hyperlipidemia. Their administration reduced oxidative stress and liver enzyme levels (AST, ALT, and ALP) and improved lipid profiles, indicating their potential as therapeutic agents against glucocorticoid-related metabolic disturbances. The enhanced effectiveness observed in the combined treatment groups likely reflects synergistic activity between these compounds.
Identification of multiple cardiotonic steroids in faecal material of untreated humans and rat strains.
Masso ZF, Ebrahim Mullah HB, Thiba A … +6 more , Dinat S, Nweke EE, Norton GR, Woodiwiss AJ, Cromarty AD, Candy GP
Steroids · 2026 Mar · PMID 41512948 · Publisher ↗
UNLABELLED: Endogenous cardiotonic steroid (CTS) concentrations are raised in cardiovascular diseases. CTSs undergo gastro-hepatobiliary recirculation, with the gut being an important route of elimination, yet the presen...
UNLABELLED: Endogenous cardiotonic steroid (CTS) concentrations are raised in cardiovascular diseases. CTSs undergo gastro-hepatobiliary recirculation, with the gut being an important route of elimination, yet the presence of CTSs in faecal material is seldom reported. This study investigated methods to extract and identify the presence of CTSs in faecal material of rats and humans without prior treatment. METHODS: Freeze-dried faecal material from different untreated rat strains was extracted using various solvents, with separation and identification of CTSs using HPLC/MS. Preliminary results were obtained from human faecal material. RESULTS: Multiple CTSs were identified in faecal material, with marinobufagenin (MBG) predominant. Telocinobufagin was only detected in certain rat strains, whereas the extraction methods used did not recover ouabain. MBG and digoxin were elevated in Dahl salt sensitive rats fed supplementary salt. Bufalin was present in most spontaneously hypertensive rats (SHRs) but was not detectable in Wistar Kyoto rats (WKY). Conversely, digitoxin was detected in most WKYs but only few SHRs. Levels of digitoxin and bufalin remained relatively constant over 24 days in untreated rats. Solvent selection was critical in determining the CTSs extracted from human faecal material. CONCLUSIONS: Multiple CTSs were detected in faecal material of untreated rats and humans. Steroids varied between rat strains and aligned with phenotype. Extraction requires further solvent optimisation and the use of tandem MS/MS is essential to reliably detect the profile of CTSs present. Analysis of CTSs present in readily available faecal material will enable studies to determine relationships between CTSs, the microbiome and disease progression.
l-arginine mitigates endocrine and spermatogenesis disruptions in cisplatin-exposed male Wistar rats by modulating iNOS/NO/NF-kB and Nrf2/HO-1 signaling.
Obembe OO, Oyeniyi GA, Ashonibare PJ … +3 more , Akhigbe TM, Ashamu EA, Akhigbe RE
Steroids · 2026 Feb · PMID 41421684 · Publisher ↗
BACKGROUND: Even though cisplatin is highly effective in cancer treatment, its toxicity to non-target organs, such as the testes, remains a concern. Studies have shown that cisplatin induces testicular toxicity by activa...
BACKGROUND: Even though cisplatin is highly effective in cancer treatment, its toxicity to non-target organs, such as the testes, remains a concern. Studies have shown that cisplatin induces testicular toxicity by activating an oxido-inflammatory response. Conversely, arginine exerts antioxidant and anti-inflammatory properties. AIM: Hence, the current study assessed the impact of arginine on cisplatin-induced testicular toxicity. In addition, the involvements of iNOS/NO/NF-kB and Nrf2/HO-1 signaling, which are key pathways in cisplatin toxicity, were probed. MATERIALS AND METHODS: Twenty-four male Wistar rats were acclimatized for two weeks and then randomized into 4 equal groups; control, arginine-treated, cisplatin-treated, and cisplatin + arginine-treated. RESULTS: Arginine significantly attenuated cisplatin-induced reductions in sperm concentration, motility, and viability and increased the percentage of abnormal sperm morphology. More so, arginine markedly suppressed cisplatin-induced reductions in daily and total spermatid production, and circulating levels of GnRH, FSH, LH, and testosterone. Additionally, arginine improved cisplatin-induced distortion in testicular histology. These findings were associated with arginine-driven mitigation of cisplatin-induced rise in MDA, TNF-α, IL-6, IL-1β, iNOS, and NF-kB and cisplatin-induced decline in GSH, TAC, IL-10, NO, and Nrf2 levels and GR, SOD, catalase, and HO-1 activities. CONCLUSION: Summing up, arginine mitigated cisplatin-induced testicular endocrine and spermatogenesis disruption via the modulation of iNOS/NO/NF-kB and Nrf2/HO-1 signaling.
Novel heterosteroids induce anabolic effects in human skeletal muscle cells: An integrated analysis of anabolic and catabolic signaling pathways.
Pérez-Pérez LF, Guerrero-Luna G, Mendoza-Montalvo A … +7 more , Olazo-Márquez N, López-Bartolo M, González-Pérez PP, Juárez JR, Bernès S, Cárdenas-García M, Hernández-Linares MG
Steroids · 2026 Feb · PMID 41397576 · Publisher ↗
The aim of this study was to investigate the anabolic potential of novel heterosteroids in human skeletal muscle cells. A library of new heterosteroids was synthesized by selectively modifying the A and B rings of steroi...
The aim of this study was to investigate the anabolic potential of novel heterosteroids in human skeletal muscle cells. A library of new heterosteroids was synthesized by selectively modifying the A and B rings of steroidal sapogenins (diosgenin, sarsasapogenin, and hecogenin), with six library members (S1, D3, D5, D7, D8 and D13) subsequently tested in vitro. Compound selection was based on computational modeling intracellular signaling pathways regulating muscle hypertrophy and atrophy, coupled with pharmacological potential evaluation using cheminformatics tools. The anabolic activity of these compounds was evaluated in the ATCC PCS-950-010 HSkM cell line, which represents normal human skeletal muscle cells. Among the compounds tested, D5 and D7 increased protein synthesis by approximately 22 % and 14 %, respectively. Compound D8 exhibited the most pronounced effect, increasing cell proliferation by approximately 50 %. Molecular docking and microarray analyses confirmed that D8 stimulates anabolism through AKT, ERK and MAPK activation, revealing the complex interplay between MAPK, PI3K and GPCR signaling pathways in the regulation of muscle cell proliferation. These findings suggest that compounds D8, D5, and D7 warrant further investigation in the context of muscle anabolism as potential therapeutic agents for targeting muscle atrophy.
The effects of tamoxifen and its metabolites on circulating estrogen metabolites among pre- and postmenopausal women.
Ghosh R, Pfeiffer RM, Ramin C … +7 more , Xu X, Turner PC, He X, Troisi R, Fan S, Gierach GL, Dallal CM
Steroids · 2026 Feb · PMID 41386485 · Full text
PURPOSE: Circulating estrogen metabolites of the 2-, 4- or 16-hydroxyestrone (OH) pathways may be differentially associated with breast cancer risk due to varying estrogenic and genotoxic activity. However, little is kno...
PURPOSE: Circulating estrogen metabolites of the 2-, 4- or 16-hydroxyestrone (OH) pathways may be differentially associated with breast cancer risk due to varying estrogenic and genotoxic activity. However, little is known about the influence of tamoxifen, an effective endocrine therapy, or its metabolites on estrogen metabolism. METHODS: Among women referred to tamoxifen therapy, 15 circulating estrogens and estrogen metabolites (EMs) were measured at baseline (pre-tamoxifen) and 12 months post-tamoxifen initiation using liquid chromatography-tandem mass spectrometry. Changes in EMs were assessed among women postmenopausal at baseline (n = 23) using paired t-tests. Using linear regression, cross-sectional associations between circulating tamoxifen, its three metabolites, and EMs were assessed 12-months post-tamoxifen among pre- (n = 33) and postmenopausal women (n = 27; includes four women who transitioned to postmenopausal during follow-up). RESULTS: Twelve months post-tamoxifen initiation, mean total EM concentrations decreased by 13.8% among postmenopausal women, primarily driven by decreases in 2-OH (15.3%) and 16-OH (17.2%) metabolites (p < 0.05). Among women premenopausal at 12-month follow-up, circulating tamoxifen was positively associated with estrone (β = 1.24), estradiol (β =1.39), 2-OH metabolites (2-OHE1: β = 0.72, 2-ME1: β = 1.15), and all 16-OH metabolites (p < 0.05). The tamoxifen metabolite, endoxifen, was positively associated with estrone (β = 10.1) and estradiol (β = 12.4), and select 2-OH and 16-OH metabolites (p < 0.05). Positive associations were also observed between 4-hydroxy-tamoxifen and estrone, 2-OHE1, 2-ME1, 4-ME1, and E3 (p<0.05). Among postmenopausal women, only N-desmethyltamoxifen was significantly associated with 3ME1 (β = 0.18, p = 0.02). CONCLUSION: Tamoxifen and its metabolites were associated with changes in circulating EMs. Further research is needed to understand tamoxifen-induced EM changes in breast cancer prevention and management.
Endoplasmic reticulum stress and steroidogenic dysfunction in Leydig cells: Molecular mechanisms of UPR-mediated testosterone regulation.
Martin LJ
Steroids · 2026 Feb · PMID 41371596 · Publisher ↗
This review aims to synthesize current evidence on how endoplasmic reticulum (ER) stress affects steroidogenic function in Leydig cells. It explores the mechanisms by which ER stress activates the unfolded protein respon...
This review aims to synthesize current evidence on how endoplasmic reticulum (ER) stress affects steroidogenic function in Leydig cells. It explores the mechanisms by which ER stress activates the unfolded protein response (UPR) and autophagy pathways, ultimately influencing testosterone production and cellular homeostasis. The central research question addresses how ER stress-induced signaling modulates the transcriptional regulation of key steroidogenic enzymes and contributes to age-related declines in androgen synthesis. A comprehensive literature review was conducted using recent findings from molecular, cellular, and animal studies focusing on ER stress signaling in Leydig cells. Studies examining the roles of UPR branches (PERK, IRE1, and ATF6), autophagy pathways, and pharmacological or natural compounds modulating ER stress were analyzed to identify the regulatory mechanisms being involved and potential therapeutic implications. Evidence indicates that unresolved ER stress impairs testosterone biosynthesis by suppressing the expression of genes related to steroidogenesis. Specifically, activations of XBP1, ATF4 and ATF6, as well as their nuclear translocations, may lead to the transcriptional repression of these genes. Conversely, pharmacological ER stress inhibitors and natural antioxidants may restore these protein levels, enhance testosterone production, and improve Leydig cell function. A thorough understanding of the UPR and autophagy in Leydig cells is critical for addressing male reproductive health. ER stress is established as a key factor in the pathophysiology of impaired steroidogenesis. Therefore, targeting these stress response pathways presents a promising strategy for developing novel therapeutic interventions for testosterone deficiency and associated reproductive disorders.
The impact of reproductive steroids on autosomal dominant polycystic kidney disease progression in women.
Hasan NS, Thomas W
Steroids · 2026 Feb · PMID 41354137 · Publisher ↗
Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by the growth of fluid filled cysts in the kidney. ADPKD arises due to a heritable mutation in the polycystic kidney disease 1 gene (PKD1) a...
Autosomal dominant polycystic kidney disease (ADPKD) is a disease characterized by the growth of fluid filled cysts in the kidney. ADPKD arises due to a heritable mutation in the polycystic kidney disease 1 gene (PKD1) and polycystic kidney disease 2 gene (PKD2) ultimately leading to kidney failure. Incidence in males and females is equivalent, but differences arise in progression. This review brings together various studies regarding the impact of cyclic hormone changes on ADPKD progression, bringing attention to gaps in knowledge that needs to be addressed. Circulating hormones play a crucial role in the pathogenesis of the disease, particularly the renin angiotensin system. The physiological actions of estrogen tend to have a protective effect on the kidney, contributing to a slowed progression in females. The hormonal changes of the menstrual cycle and at menopause result in changes in pathology via blood pressure fluctuation, promotion of renal repair and prevention of renal scarring and damage. Signaling pathways that are involved in cyst growth such as cAMP, mTOR, MAPK/ERK, and PI3K/Akt are modulated by estrogen, providing insights into potential mechanisms. Estrogen-based hormonal therapy is being investigated for its efficacy in improving renal function post menopause.
An unexpected oxidative E/F ring opening in the side chain of steroid sapogenins produced by silica gel supported Jones Reagent.
Hernández-Martínez JE, Ruíz-Pérez KM, Sanchez-Flores J … +1 more , Iglesias-Arteaga MA
Steroids · 2026 Feb · PMID 41318016 · Publisher ↗
In contrast with previous results in which the spiroketal side chain of steroid sapogenin has proven to be unreactive to Jones Reagent, treatment these sapogenins with silica gel-supported Jones Reagent triggered the oxi...
In contrast with previous results in which the spiroketal side chain of steroid sapogenin has proven to be unreactive to Jones Reagent, treatment these sapogenins with silica gel-supported Jones Reagent triggered the oxidative opening of the spirostanic side chain producing moderate to good yields of sapogenoic acids that bear carbonyl functions at C-16 and C-22 and a C-26 carboxylic group. Based on these findings, a procedure that allows the synthesis of sapogenoic acids minimizing contamination by chromium salts was designed.
LC-MS/MS quantitation of the primary reduced metabolites of progesterone in serum during the third trimester of human pregnancy reveals a potential role for 20β-hydroxyprogesterone and 5β-dihydroprogesterone in functional progesterone withdrawal.
Hinchliffe E, Heazell A
Steroids · 2026 Jan · PMID 41297826 · Publisher ↗
Progesterone (P4) is an essential steroid hormone synthesised by the placenta required for the maintenance of pregnancy. In humans, the metabolism of P4 has been implicated in functional P4 withdrawal prior to parturitio...
Progesterone (P4) is an essential steroid hormone synthesised by the placenta required for the maintenance of pregnancy. In humans, the metabolism of P4 has been implicated in functional P4 withdrawal prior to parturition. We have developed a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitation in human serum of pregnenolone, P4 and its four primary reduced metabolites; 20α-hydroxyprogesterone (20α-OHP), 20β-hydroxyprogesterone (20β-OHP), 5α-dihydroprogesterone (5α-DHP) and 5β-dihydroprogesterone (5β-DHP). Following solid phase extraction, chromatographic baseline separation of each steroid was achieved using a biphenyl stationary phase within a 10.0 min runtime, followed by MS detection on a Sciex 6500+. The LC-MS/MS method was validated in accordance with published guidelines, confirming acceptable analytical performance pertaining to linearity, imprecision, accuracy, sensitivity, matrix effects, specificity and carryover. The method was applied to a large cohort of third trimester pregnancies with verified uncomplicated neonatal outcomes. Maternal circulating concentrations of P4, 20α-OHP, 20β-OHP, and 5α-DHP positively correlated with fetal gestational age. The ratio of P4:20β-OHP declined significantly throughout the third trimester, whilst the ratio of P4:5β-DHP increased at full term from 40 weeks' gestation. These findings may indicate a substantive role for β-reduction of P4 in the mechanics of functional P4 withdrawal, either via depletion of the overall pool of bioactive P4 or competitive binding of these metabolites to the P4 receptor in maternal and fetal tissue. Additionally, detailed characterisation of the normal maternal steroidome will facilitate the study of dysregulated placental steroidogenesis, which has been implicated in the pathogenesis of the major obstetric syndromes causing poor pregnancy outcomes.
Semi-synthetic sapogenin derivatives inhibit inflammation-induced tumorigenic signaling alterations in prostate carcinogenesis.
Debelec-Butuner B, Ozturk MB, Tag O … +2 more , Akgun IH, Bedir E
Steroids · 2026 Jan · PMID 41290083 · Publisher ↗
Prostatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of anti-inflammat...
Prostatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of anti-inflammatory drugs could provide a valid contribution to PCa prevention and treatment. In our research, we explored semi-synthetic derivatives of cycloastragenol (CA) and astragenol (AG) to assess their potential to inhibit inflammation-mediated tumorigenic signaling. Building on our previous findings, which demonstrated their inhibitory activity on NFκB, we discovered that these molecules also suppress inflammation-induced cell proliferation and migration through distinct mechanisms. They effectively alleviated inflammation by reducing levels of ROS, NO, and VEGF expression. Furthermore, these molecules partially restored the expression of AR and the tumor suppressor NKX3.1, both of which are critical in prostate tumorigenesis within an inflammatory microenvironment. They also reversed inflammation-induced activation of Akt and β-catenin signaling, suggesting their potential to inhibit inflammation-related prostate tumorigenesis. Our study further demonstrated that these molecules exhibited dose-dependent effects on inducing cell cycle arrest and apoptosis, as evidenced by increased p21 and decreased BCL-2 protein levels, leading to activated cell death and suppressed cellular migration. In conclusion, these semi-synthetic sapogenol derivatives demonstrate significant potential as anti-inflammatory and anticancer agents, offering a promising approach for targeting prostatic inflammation and inflammation-driven prostate carcinogenesis.
Antifungal ergostane-type steroids from endophytic fungus Xylaria sp. VDL4.
Yao J, Lu LH, Wei SY … +7 more , Wu T, Yang W, Wang WH, Yang FZ, Li YX, Zhao P, Zhu GL
Steroids · 2026 Jan · PMID 41285194 · Publisher ↗
Three ergostane-type steroids, including one rare C-29 methylated xylarstane A (1) and one C22,23-epoxied xylarstane B (2), along with one reported compound 3, were isolated from the endophytic fungus Xylaria sp. VDL4 ha...
Three ergostane-type steroids, including one rare C-29 methylated xylarstane A (1) and one C22,23-epoxied xylarstane B (2), along with one reported compound 3, were isolated from the endophytic fungus Xylaria sp. VDL4 harbored within the medicinal plant Vaccinium dunalianum. The structures of novel compounds were elucidated through comprehensive spectroscopic analysis, DP4-validated theoretical C nuclear magnetic resonance (NMR) calculations, and electronic circular dichroism (ECD) calculations. The antifungal activities of the isolates against four phytopathogens were assessed in vitro. Compounds 1 and 3 exerted significant inhibition against Alternaria solani and Botrytis cinerea respectively, both with minimal inhibitory concentration (MIC) of 12.5 μg/mL, comparing with the positive control (Carbendazim and Thiabendazole, MICs = 12.5-25.0 μg/mL).
Exposure-response of serum biomarkers to vamorolone, a dissociative corticosteroidal anti-inflammatory drug, in 4- to <7-year children.
Mummidivarpu S, Dang UJ, Ziemba M … +19 more , Hathout Y, Clemens PR, Damsker J, Hagerty L, Jusko WJ, Smith EC, Mah JK, Guglieri M, Nevo Y, Kuntz N, McDonald CM, Ryan MM, Castro D, Finkel RS, Conklin LS, McCall JM, Nagaraju K, van den Anker J, Hoffman EP
Steroids · 2026 Jan · PMID 41265551 · Publisher ↗
OBJECTIVES: Corticosteroid agonists of the glucocorticoid receptor are a mainstay of therapeutics for pro-inflammatory conditions. Vamorolone is a novel partial agonist that is differentiated from the other members of th...
OBJECTIVES: Corticosteroid agonists of the glucocorticoid receptor are a mainstay of therapeutics for pro-inflammatory conditions. Vamorolone is a novel partial agonist that is differentiated from the other members of the corticosteroid class by non-metabolism by 11β-hydroxysteroid dehydrogenases, antagonism of the mineralocorticoid receptor, and differential co-factor binding. Our objective was to define the pharmacodynamic response of serum proteins to vamorolone. METHODS: Clinical trial participants with Duchenne muscular dystrophy (4 to <7 yr; n = 39; mean [SD] age = 5.3 [1.0]) enrolled in a multiple ascending dose study of vamorolone were studied (24-fold dose range). Dose-response and exposure-response of 1,305 serum proteins were defined by intra-subject longitudinal changes (baseline vs. Day 14). RESULTS: Dose-response analysis identified 159 of 1,305 serum proteins as dose-responsive to vamorolone (12 % of proteins tested; 20 % increased, 80 % decreased). Two inflammatory networks showed drug-responsive suppression. One centered on extracellular serine proteases and lymphotoxins (PI3, KLK7, KLK8, KLK11, lymphotoxins A, B) converging on NFκB. The second centered on cytokines (CCL22/MDC, CCL21, CCL14, CXCL12) and IL23 signaling. In the IL23 network, acutely responsive anti-inflammatory proteins included increases of an inhibitor of IL17 signaling (IL17RC) and decreases of IL23 (IL12B:IL23A). A protein associated with resistance to environmental microbes, PTP1C, showed strong induction and is a novel candidate for aspects of corticosteroid efficacy. Two networks of cell-associated proteins were identified as drug responsive that may represent muscle tissue response (efficacy): connective tissue remodeling upstream of Notch signaling, and plasma membrane proteins impinging on AKT1 signaling. CONCLUSION: The serum proteome pharmacodynamics of the response to vamorolone was defined.
Discovery of dihydrobetulinic acid as a potent small molecule CD73 inhibitor.
Wang H, Zhang Y, Lou C … +5 more , Chang X, Yang H, Zhang D, Ma H, Miao Z
Steroids · 2026 Jan · PMID 41265550 · Publisher ↗
Betulinic acid (BA) is a pentacyclic triterpene compound with various biological activities. Herein, we designed and synthesized a series of dihydrobetulinic acid (DHBA) and its derivatives for the discovery of potent ec...
Betulinic acid (BA) is a pentacyclic triterpene compound with various biological activities. Herein, we designed and synthesized a series of dihydrobetulinic acid (DHBA) and its derivatives for the discovery of potent ecto-5'-nucleotidase (CD73) inhibitors. Biological evaluation of DHBA and its derivatives led to the disclosure of three active compounds DHBA, ZM792 and ZM905. Further investigation of antitumor immunity revealed that DHBA could effectively restore the function of CD4 T cells. These results provide novel insights for future endeavors in developing novel agents derived from natural product targeting CD73 enzyme.
In vitro metabolic profiling of 6-chloro-testosterone and 6-ene-testosterone by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-time of flight (GC-TOF) mass spectrometry.
Martínez Brito D, Stacchini C, Colamonici C … +3 more , Curcio D, Botrè F, de la Torre X
Steroids · 2026 Jan · PMID 41265549 · Publisher ↗
Among the phase-I reactions of 6-chloro-testosterone (6-CT), the reductive and oxidative dehalogenation, as well as the dehydrogenation, have been described here. One of the metabolic products could be the 6-ene-testoste...
Among the phase-I reactions of 6-chloro-testosterone (6-CT), the reductive and oxidative dehalogenation, as well as the dehydrogenation, have been described here. One of the metabolic products could be the 6-ene-testosterone (6-ene-T). The goal of this work was to study the in vitro metabolism of 6-CT and 6-ene-T after incubation with human liver microsomes (HLM), analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time-of-flight-mass spectrometry (GC-TOF). 6-CT showed a more extensive metabolism compared to 6-ene-T, with the formation of a larger number of metabolites. In contrast, 6-ene-T, which potentially preserves the C6C7 double bond in most of its metabolites, showed fewer metabolites. Therefore, after incubation with HLM, the main metabolic routes of 6-ene-T are the oxidation of the hydroxyl group on C17β, retaining the double bond C6C7 to form 6-ene-androstenedione, and the hydroxylation on C6. On the other hand 6-CT metabolism produced chlorinated and non-chlorinated metabolites as a result of the phase I reactions which included oxidation, reduction, hydroxylation and (oxidative and reductive) dehalogenation. Specifically for 6-CT, it should be considered that the introduction of a chlorine atom in the 6α position of T may lead to a shift in the metabolic pathway, favoring the formation of 5β-reduced metabolites over 5α-reduced metabolites, due to the steric and electronic effects of the chlorine atom on the interaction between the steroid molecule and the 5α-reductase enzyme.
Protective effect of vitamin D on high-fat-diet-induced metabolic dysfunction-associated steatotic liver disease in mice.
Mohamed AA, Hafez W, El-Feky S … +14 more , Khalil MG, Soliman AS, Nasraldin K, Ibrahim IM, Hegazy HA, Shaheen W, Abbas AM, Shaheen H, Abdelmalak MF, Azzam HN, Ezzat O, Hassan NAIF, Dulaimi OA, Madkour NK
Steroids · 2026 Jan · PMID 41260319 · Publisher ↗
BACKGROUND: Genetics, inflammation, and nutrition contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). AIM: This preclinical study evaluated the protective effect of vitamin...
BACKGROUND: Genetics, inflammation, and nutrition contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). AIM: This preclinical study evaluated the protective effect of vitamin D supplementation against high-fat-diet-induced MASLD in a mouse model and compared physiological, inflammatory, and molecular responses across high-fat and low-fat dietary regimens, with and without vitamin D co-administration. METHODS: Forty-five healthy male albino Swiss mice (aged 6 weeks; 30 ± 10 g) were randomly assigned to five groups (n = 9 each): control (standard diet), HFD (high-fat diet), HFD + vitamin D, LFD (low-fat diet), and LFD + vitamin D. Vitamin D (20 000 IU/kg/week) was administered via drinking water for 12 weeks. Body weight, visceral adiposity, and liver indices were recorded, while serum biochemical markers, inflammatory cytokines, and expression of Toll-like receptor 7 (TLR7) and microRNA-155 (miR-155) were analyzed at endpoint. RESULTS: HFD-fed mice exhibited marked increases in ALT (51.44 ± 9.68 U/L), AST (56.67 ± 13.29 U/L), ALP (135.01 ± 16.19 U/L), AFP (28.56 ± 5.31 ng/mL), CRP (20.87 ± 5.56 mg/L), total cholesterol (225.00 ± 27.16 mg/dL), LDL (137.56 ± 28.66 mg/dL), and triglycerides (210.56 ± 28.71 mg/dL), accompanied by reduced HDL (30.24 ± 9.86 mg/dL) compared with controls. Pro-inflammatory cytokines TNF-α (28.33 ± 2.96 pg/mL), IL-6 (121.78 ± 8.98 pg/mL), and the expression of TLR7 (2.92 ± 0.83) and miR-155 (2.75 ± 0.77) were significantly elevated relative to normal-fed mice (miR-155: 0.84 ± 0.26). Vitamin D supplementation significantly ameliorated these metabolic and inflammatory disturbances. CONCLUSIONS: Vitamin D supplementation mitigated HFD-induced hepatic injury, dyslipidemia, and inflammatory activation by modulating the miR-155/TLR7 axis. These findings highlight vitamin D as a potential adjunctive strategy for preventing or attenuating MASLD progression under high-fat dietary conditions.
Dehydroepiandrosterone impact on smooth muscle contractile activity by a nongenomic action.
Perusquía M
Steroids · 2026 Jan · PMID 41242676 · Publisher ↗
Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates; however, its levels decline with age in both men and women. Numerous studies have documented diverse biological activities of DHEA. This art...
Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates; however, its levels decline with age in both men and women. Numerous studies have documented diverse biological activities of DHEA. This article reviews the current understanding of how DHEA regulates the contractile function of vascular and nonvascular smooth muscle (SM), specifically examining its relaxant properties mediated through nongenomic mechanisms. It summarizes both older and recent findings on DHEA and its role in regulating SM contractile activity. Moreover, it also discusses the potential mechanisms underlying its relaxation effects, including the structural-functional differences in the DHEA molecule and its ability to induce relaxation in various types of SM. Overall, DHEA introduces a novel aspect to the regulation of functional processes involved in SM contractile activity.
The influence of the route of drug administration on the metabolic profile of trenbolone in doping control urine samples.
Krombholz S, Piper T, Lagojda A … +2 more , Kühne D, Thevis M
Steroids · 2026 Jan · PMID 41224119 · Publisher ↗
Advances in analytical techniques have markedly improved the detection of anabolic-androgenic steroids (AAS) in doping controls. This represents a major success for anti-doping efforts, but at the same times raises conce...
Advances in analytical techniques have markedly improved the detection of anabolic-androgenic steroids (AAS) in doping controls. This represents a major success for anti-doping efforts, but at the same times raises concerns about inadvertent exposure - not limited to oral ingestion, but also via dermal contact or mucosal absorption. Evaluating the plausibility of such scenarios can be complex, not least because these routes of drug intake can also be deliberately used for doping purposes. Analytical data on transdermal or mucosal absorption and elimination of AAS can be valuable here, particularly regarding the metabolite pattern in urine samples that might help to assess the route of drug delivery. This study investigated the urinary excretion profile of trenbolone and its metabolites after oral, transdermal and buccal administration in healthy male volunteers. Urine samples collected over a period of one week following the administration of 10 mg of trenbolone were analyzed by LC-HRMS, with regard to potential differences in the metabolite profile across the different routes of drug intake. Major trenbolone metabolites were detectable in the urine samples of all participants, however the detection windows varied strongly: Buccal resorption resulted in faster elimination, whereas transdermal application resulted in prolonged detectability, compared to oral administration. A cysteine-conjugated metabolite (M15-cys) was identified that showed higher abundances following transdermal and buccal administration, suggesting its potential as a marker for non-oral intake. In light of the growing importance of transdermal uptake of doping agents, these results provide valuable data for interpreting doping control findings, potentially also relevant for structurally related AAS.
Cortisol-to-cortisone and testosterone-to-androstenedione concentration ratios in nails: Their determination methods based on LC/MS/MS and differences from the serum concentration ratios in the literature.
Ishikawa H, Tanaka S, Shibata K … +1 more , Higashi T
Steroids · 2026 Jan · PMID 41187891 · Publisher ↗
A fingernail clipping is expected to be a specimen suited for the detection of the medium-to-long term abnormal production of steroids. There are reports demonstrating that the concentration ratios of cortisol (F) to cor...
A fingernail clipping is expected to be a specimen suited for the detection of the medium-to-long term abnormal production of steroids. There are reports demonstrating that the concentration ratios of cortisol (F) to cortisone (E) and testosterone (T) to androstenedione (AD) in nails are significantly different from those in serum. However, the concentration ratios in the nails were determined with a small number of samples in some instances and differed from study to study, in addition to which, their gender differences remain poorly understood. Determining the differences in the concentration ratios between the nails and serum with a sufficient number of samples by gender and discussing a factor causing these differences will help for an accurate interpretation of the results in the nail-based steroid tests. In this study, we first developed and validated liquid chromatography/electrospray ionization-tandem mass spectrometry methods for determining the F/E and T/AD ratios in thumbnail clippings, then demonstrated that the F/E (in both sexes) and T/AD (in male) ratios in the nails were significantly lower than those in the serum reported in the literature. We found that steroids which are present at the higher concentrations in the nail than expected from their serum concentrations, such as E and AD, are bound to albumin at a high rate in the serum. As the affinities of corticoids and androgens to albumin are low (Ka, 10-10 M), we concluded that the albumin-bound fractions can be the sources of the nail-incorporated steroids as well as the free fractions.
α-Silyl substituted vinyl carbanions in the synthesis of brassinolide and castasterone.
Barysevich MV, Kazlova VV, Chaschina NM … +4 more , Akalovich MD, Syakhovich VE, Zhabinskii VN, Khripach VA
Steroids · 2025 Dec · PMID 41167517 · Publisher ↗
A concise synthesis of brassinolide and castasterone has been accomplished herein. The strategy relies on the addition of α-silyl substituted vinyl carbanions to steroidal C-22 aldehydes with pre-formed functionalities i...
A concise synthesis of brassinolide and castasterone has been accomplished herein. The strategy relies on the addition of α-silyl substituted vinyl carbanions to steroidal C-22 aldehydes with pre-formed functionalities in the cyclic part. Commercially available brassinosteroids were used as a starting material. The key step of the present synthesis was the opening of the 23,24-epoxide with MeAl in the presence of PhP as a Lewis base, which enhances the formation of a more nucleophilic alkylating agent. It was shown why the use of MeAl is incompatible with the 3α,5-cyclo steroids, which are often employed as intermediates in the synthesis of brassinosteroids.
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