Search Results (120)

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m² (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article

Background/Objectives: Vitamin D₃ is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D₃ and 1,25(OH)₂D₃, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Methods: Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D₃ and 1,25(OH)₂D₃ or the combination of vitamin D₃, 25(OH)D₃ and 1,25(OH)₂D₃. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D₃ release under basal and isoproterenol-stimulated conditions using ³H-vitamin D₃ and scintillation counting. Results: Vitamin D₃ uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D₃ and 1,25(OH)₂D₃ peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D₃ release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Conclusions: Adipocytes selectively retain vitamin D₃ while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies—particularly in individuals with excess adiposity—may improve bioavailability and metabolic efficacy. Full article

Background/Objectives: Pomegranate (Punica granatum) peel, often discarded as waste, contains abundant bioactive compounds such as polyphenols, vitamins, flavonoids, tannins, anthocyanins, and many more. This contributes to remarkable bioactivities, including anticancer, anti-inflammatory, antioxidant, antibacterial, and antifungal properties. Pancreatic cancer is a deadly cancer with a 9% survival rate. Its aggressiveness, invasiveness, quick metastasis, and poor prognosis significantly decrease the survival rate. Thus, we aim to explore pomegranate peel as a possible alternative medication for treating pancreatic cancer through virtual methods. Methods: Firstly, bioactive compounds were collected from multiple databases and screened for oral bioavailability (OB) ≥ 0.3 and drug likeness (DL) ≥ 0.18 scores. Simultaneously, network pharmacology was employed to extract the most probable targets for pancreatic cancer. Further computational analyses were performed, including molecular docking, molecular dynamics simulation, and in silico pharmacokinetics evaluation. Results: Consequently, the top 10 key targets from network analysis were AKT1, IL6, TNF, SRC, STAT3, EGFR, BCL2, HSP90AA1, HIF1A, and PTGS2. However, only AKT1, EGFR, BCL2, HSP90AA1, and PTGS2 exhibited strong binding affinities with pomegranate compounds, which are significantly declared in affected cells to enhance cancer progression. Outcomes from molecular dynamics simulations, particularly RMSD, RMSF, hydrogen bonding, and radius of gyration (Rg), confirmed stable interactions between 1-O-Galloyl-beta-D-glucose, epicatechin, phloridzin, and epicatechin gallate with respective target proteins. Conclusions: This suggests that pomegranate peels hold anticancer bioactive compounds for treating pancreatic cancer. Surprisingly, most compounds adhere to Lipinski’s and Pfizer’s rules and display no toxicity. However, as this study relies entirely on computational methods, experimental validation is necessary to confirm these findings and assess real-world efficacy and potential side effects. Full article

Acute pancreatitis (AP) is primarily caused by inflammation and immunological responses, both of which are regulated by vitamin D. The purpose of this study was to examine the correlation between the severity of AP and vitamin D levels, including its total, free, and bioavailable forms. Eighty individuals with AP were enrolled in this study. Serum levels of free 25(OH)D₃, bioavailable 25(OH)D₃, and total 25-hydroxyvitamin D 25(OH)D₃ were assessed. The severity of the disease course was assessed by scoring systems (Revised Atlanta classification, Ranson score, CTSI). Vitamin D deficiency was common in AP patients, with 31.3% being categorized as deficient (<50 nmol/L) and 27.5% having a severe deficiency (<30 nmol/L). Compared to patients with adequate vitamin D status, those with lower vitamin D levels had a significantly higher risk of developing moderate-to-severe AP (44.7% vs. 14.3%, p = 0.029). Patients with severe vitamin D insufficiency were the only ones who experienced severe AP. Clinical outcomes showed similar correlations: patients with significant vitamin D deficiency had longer hospital stays (mean of 12.1 ± 5.3 days vs. 7.8 ± 3.4 days, p = 0.018) and higher rates of ICU admission (31.8% vs. 8.0%, p = 0.007). Low levels of total, free, and bioavailable vitamin D were significantly associated with the severity of AP and ICU admission. Free, bioavailable, and total vitamin D were correlated with the severity of acute pancreatitis. All severe cases occurred in patients with severe vitamin D deficiency. Given the observational design, these associations require confirmation in interventional or mechanistic studies. Full article

Vitamin E is widely used in cosmetics and dermatological applications for its antioxidant, anti-inflammatory, and healing properties, yet its industrial use is limited by poor stability and bioavailability. To address these challenges, this study developed zein-based microstructures encapsulating vitamin E using electrohydrodynamic (EHD) techniques and evaluated how zein concentration affects morphology and release behavior. The SEM analysis showed that biopolymer (zein) concentration significantly affects microstructure morphology. At low concentrations (1%, 5%, and 15% (w/v)), micro/nanoparticles are formed, and high concentrations (30% (w/v)) yielded only fibers. The average size of the structures produced with zein (1–15% w/v) ranged from 0.38 to 0.90 µm, as measured using the program ImageJ (v1.54d). Structures containing vitamin E were generally smaller than those without. For electrospun fibers made with 30% zein, diameters ranged from 0.49 to 0.74 µm, with vitamin E-containing fibers also being thinner. Conductivity also influenced morphology; higher conductivity developed fibers, while lower conductivity formed particles. The solution with 15% (w/v) zein + 1% (w/w) vitamin E showed a conductivity of 1276 μS, similar to the 15% zein solution (1280 μS), indicating that vitamin E addition had no significant effect on conductivity. Release assays revealed that structures produced with low zein concentrations led to immediate release, while structured made with higher concentrations, prolonged release. A preliminary cosmetic formulation test has been conducted. The vitamin E microstructures were successfully incorporated into aloe vera hydrogel and coconut oil to show their potential for cosmetic applications. Full article

Torreya grandis kernels, with their long cultivation history and significant economic value, have gained attention for their characteristic chemical components. This review systematically evaluates recent research on the chemical constituents and biological activities of T. grandis kernels. The key highlights include the following. (1) Chemical composition: This review details their unique fatty acid profile, particularly the high content of unsaturated fatty acids and rare polymethylene-interrupted polyunsaturated fatty acids such as sciadonic acid. It also examines polyphenolic compounds (flavonoids, phenolic acids, and biflavonoids like kayaflavone) and volatile components dominated by D-limonene. Other constituents, such as proteins, amino acids, vitamins, and minerals, are covered. Advanced analytical techniques (Gas Chromatography–Mass Spectrometry, GC-MS; Liquid Chromatography–Tandem Mass Spectrometry, LC-MS/MS) for component identification are discussed. (2) Biological activities: This review summarizes the major biological activities of T. grandis kernel extracts and key components. These include antioxidant effects (via the polyphenol-mediated NF-E2-related factor 2 (Nrf2) pathway), anti-inflammatory properties (via polymethylene-interrupted polyunsaturated fatty acids, PMI-PUFAs, inhibition of 5-LOX, and polyphenol regulation of NF-κB), and cardiovascular protection (potentially involving the AMPKα/SREBP-1c pathway). Research on gut microbiota regulation and enzyme inhibition is also outlined. (3) Research gaps and prospects: This review critically analyzes the limitations in the current research, including mechanism elucidation, component interactions, bioavailability, and safety assessment (especially the lack of human studies). Future research directions should focus on multiomics integration, structure–activity relationship analysis, standardization, and rigorous clinical evaluation. This review provides a theoretical reference for understanding the scientific value of T. grandis kernels and promoting their sustainable development. Full article

Background: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), an amphiphilic derivative of natural vitamin E, functions as both a drug efflux inhibitor and a protector against enzymatic degradation and has been widely incorporated into nano-formulations for drug design and delivery. Objective: This systematic review evaluates TPGS-based organic nanocarriers, emphasizing their potential to enhance bioavailability of active compounds which include drugs and phytochemicals, improve pharmacokinetic profiles, and optimize therapeutic outcomes, eventually overcoming the limitations of conventional oral active compounds delivery. Search strategy: Data collection was carried out by entering key terms (TPGS) AND (Micelle OR Liposome OR Nanoparticle OR Nanotube OR Dendrimer OR Niosome OR Nanosuspension OR Nanomicelle OR Nanocrystal OR Nanosphere OR Nanocapsule) AND (Oral Bioavailability) into the Scopus database. Inclusion criteria: Full-text articles published in English and relevant to TPGS, which featured organic materials, utilized an oral administration route, and included pharmacokinetic study, were included to the final review. Data extraction and analysis: Data selection was conducted by two review authors and subsequently approved by all other authors through a consensus process. The outcomes of the included studies were reviewed and categorized based on the types of nanocarriers. Results: An initial search of the database yielded 173 records. After screening by title and abstract, 52 full-text articles were analyzed. A total of 21 papers were excluded while 31 papers were used in this review. Conclusions: This review concludes that TPGS-based organic nanocarriers are able to enhance the bioavailability of various active compounds, including several phytochemicals, leveraging TPGS’s amphiphilic nature, inhibition of efflux transporters, protection against degradation, and stabilization properties. Despite using the same excipient, variability in particle size, zeta potential, and encapsulation efficiency among nanocarriers indicates the need for tailored formulations. A comprehensive approach involving the development and standardized comparison of diverse TPGS-incorporated active compound formulations is essential to identify the optimal TPGS-based nanocarrier for improving a particular active compound’s bioavailability. Full article

Acute kidney injury (AKI) is a common critical clinical disease with high morbidity and mortality rates. Ischemia-reperfusion (IR) is the main cause of AKI, and there is no effective treatment or prevention. Therefore, it is critical to screen for effective therapeutic agents and to find therapeutic targets. DKS26 is a derivative of oleanolic acid (OA) optimized for bioavailability while retaining the anti-inflammatory, antioxidant, and anti-apoptotic properties of OA. This study aimed to investigate the therapeutic effects of DKS26 on AKI and its underlying molecular mechanisms. We established an AKI model in vivo and in vitro and observed that DKS26 had an ameliorative effect on IR or H/R-induced renal tubular epithelial cell injury and reduced oxidative stress, inflammation, and apoptosis. Meanwhile, Swiss TargetPrediction and AutoDock Vina analysis revealed that DKS26 may interact with vitamin D receptors (VDR) through hydrogen bonding, suggesting that DKS26 may exert effects through VDR. In this study, we found that DKS26 treatment enhanced the stability of the VDR protein, promoted the binding of VDR to p-NF-κB P65^Ser311, reduced the entry of p-NF-κB P65^Ser311 into the nucleus, and inhibited the transcription of downstream inflammatory genes as well as their own expression, thus exerting its protective effect. In summary, these findings suggest that DKS26 may be a promising preventive strategy and provide a theoretical and experimental basis for AKI treatment. Full article

Psoriasis is an immune-related disorder that is marked by abnormal thickening of the skin, the rapid multiplication of keratinocytes, and complex interactions between immune cells and the affected areas. Although psoriasis cannot currently be cured, drugs can alleviate symptoms by regulating immune homeostasis and preventing comorbidities. There are many types of drugs to treat psoriasis: small-molecule drugs, including corticosteroids; retinoids; vitamin D analogs; and immunosuppressants, such as glucocorticoid ointment, tretinoin cream, methotrexate tablets, etc. Macromolecular biological drugs, such as Certolizumab, Secukinumab, Guselkumab, etc., include monoclonal antibodies that target various inflammatory signaling pathways. Compared with traditional small-molecule drugs, biological therapies offer better targeting and lower systemic side effects, but their high costs and invasive administration modes constrict their widespread use. Spesolimab is the latest biological agent used to target the interleukin-36 receptor (IL-36R) to be approved for market use, which significantly reduces the risk of general pustular psoriasis (GPP) flare by 84%. Additionally, there are several biological agents used to target the interleukin-23/T helper 17 cell pathway that have already entered Phase II and III clinical trials. At present, the first-line therapeutic strategy for mild psoriasis is topical administration. Systemic therapy and phototherapy are preferred for treating moderate to severe types. However, the current therapeutic drugs for psoriasis cannot completely meet the clinical needs. More advanced drug delivery systems with optimized target effects and better bioavailability are required. Nanocarriers are emerging for the delivery of proteins, nucleic acids, and cell-based therapies. In this review, we analyze the current status of psoriasis therapeutics and discuss novel delivery systems for diverse psoriasis drugs, as well as emerging cell-based therapies. We also summarize the therapeutic effectiveness of different delivery strategies. Full article

In Eastern Europe, the number of vegetarians is growing, and the number of people adhering to Christian Lents is traditionally high. However, data on the nutritional value of plant-based diets in this part of the world are limited. The aim of this study was to compare the nutritional intakes of three groups with different plant-based patterns with that of omnivores in Russia, Moscow region. The nutrient intakes of 46 vegans, 49 lacto-ovo-vegetarians, 42 people who adhered to Orthodox Great Lent, and 48 omnivores were assessed. The food frequency questionnaire method was used for data collection and analysis. The differences in absolute and calorie adjusted nutrient intakes between the groups were analysed. Additionally, a pairwise comparison of the general plant-based group (combined of the vegan, lacto-ovo-vegetarian, and Great Lent samples) and the omnivorous groups was conducted. Vegan diet was the most favourable in micronutrient composition. The intake of many micronutrients increased when switching to a more plant-based diet from a more animal-based one. The opposite association was observed only for selenium and vitamins D and B₁₂. Fasting people consumed more iodine and n-3 polyunsaturated fatty acids; however, after the calorie content was standardized, the omnivores caught up with them. The omnivores had the largest list of dietary inadequacies: they significantly more often than all other groups had inadequate intake of cholesterol (excessive), fibre, potassium, magnesium, iron, and vitamins B₁, B₆, B₉, and E (insufficient). Inadequate intake of polyunsaturated fatty acids, calcium, iodine, chromium, molybdenum, and zinc; or vitamins B₂, PP, H, B₁₂, and D was observed rather often in all the studied groups. Although, the vegan diet was richer in most micronutrients, plant products often contain substances that reduce the bioavailability of various nutrients, which can partially affect their status in the body, and, thus, may increase the need in them in vegetarians and fasters. Full article

Vitamin D is crucial for immune regulation, and its deficiency is linked to multiple sclerosis (MS). The GC gene encodes Vitamin D Binding Protein (VDBP), which regulates vitamin D transport and bioavailability. This study examines the association of GC polymorphisms (rs7041, rs4588) with MS susceptibility and their impact on 25-hydroxyvitamin D [25(OH)D] levels in a Latvian cohort. This case–control study included 296 MS patients and 253 healthy controls. Genotyping of rs7041 and rs4588 was conducted using restriction fragment length polymorphism analysis and validated by Sanger sequencing. Plasma 25(OH)D levels were measured in 131 MS patients using an enzyme-linked immunosorbent assay. Statistical analysis included Hardy–Weinberg equilibrium testing, Fisher’s exact test, allelic and genotypic frequency comparisons to assess MS risk, and the Kruskal–Wallis test for 25(OH)D level differences among genotypes. Our findings indicate that the rare rs7041-T and rs4588-A alleles, along with their corresponding haplotypes, exhibit a protective effect against MS (p < 0.001; OR = 0.65 for rs4588-A; p < 0.01; OR = 0.70 for rs7041-T). Conversely, the common rs7041-G and rs4588-C alleles were associated with an increased MS risk (p < 0.05). Individuals with the Gc1F/1F isotype had the highest average 25(OH)D levels (29.31 ng/mL), while Gc1S/2 carriers had the lowest (21.53 ng/mL). Our results indicate that GC polymorphisms may influence the susceptibility of Latvians to MS and vitamin D status. Full article

Lymphomas represent a heterogeneous group of blood tumors, generally divided into non-Hodgkin lymphoma (NHL) (90% of all lymphomas) and Hodgkin lymphoma (HL). High-grade NHL can rapidly progress so that new strategies and potentially therapeutical options are needed. Recently, it was shown that Vitamin D (VitD) inhibits the growth of cancer cells, controls their invasion and metastasis, and strengthens the antitumor activity of various types of chemotherapeutic anticancer agents. Therefore, we reviewed the recent literature about the influence of VitD and its analogues (VDAs) on the treatment and the prognosis of B-cell lymphomas. As to the in vitro studies in different cell lines, VitD3 and VDAs enhanced the anti-proliferative efficacy of various chemotherapeutics and increased the expression of VitD receptor. In in vivo studies, blood levels of VitD were considered: higher values of plasma bioavailable VitD were correlated with better progression-free survival (PFS) and overall survival (OS), while an unfavorable PFS and OS were observed in VitD deficient groups. No clinical trial was made on the analogs, thus confirming the absence of in vivo positive role of these synthetic drugs. In conclusion, higher levels of circulating VitD are related to improved OS, reduced cancer-specific mortality, and better disease-free survival. VitD and analogs showed also positive effects in in vitro studies, while only VitD was able to improve clinical parameters. Furthermore, a complex approach with plant-based diet, adequate levels for motor exercise, and/or eventual VitD supplementation could be a valuable strategy to challenge lymphomas. Full article

Many health benefits are associated with Vitamin D (VitD), although deficiency is associated with poor health outcomes and the increased risk of cancer development. For example, many tissue-specific enzymes are involved in VitD metabolism, and mutations or deletions within Vitamin D receptor (VDR) genes are known to increase the cancer risk by altering their functions or bioavailability, although less is known about these phenomena in oral cancers. Using well-characterized, commercially available oral cell lines (OKF4, HGF-1, SCC4, SCC9, SCC15, SCC25, and CAL27), the mRNA expression of P450 cytochrome VitD metabolic enzymes and receptor genes by qPCR revealed differential results. One oral cancer line (SCC15) did not express either the Vitamin D receptor (VDR) or FOK1 polymorphism and was also least affected by VitD3 administration in growth assays. In contrast, most oral cancers were missing one or more hydrolase (CYP2R1 and CYP24A1) or hydrolate (CYP27A1 and CYP27B1) enzymes. SCC25 was missing both the hydrolate enzymes and was the most inhibited in the VitD3 growth assays, while SCC4 was missing both the hydroxylase enzymes and was the least inhibited by VitD2. These associations between mRNA expression (or lack thereof) and VitD3 and VitD2 responsiveness can be used to identify molecular targets, which may lead to effective screening tools for VitD-related, complementary and alternative therapies. Full article

Vitamin D, essential for growth and health, is often deficient in Taiwan despite abundant sunlight. Plant-derived vitamin D₂ (ergocalciferol) is bioavailable, environmentally friendly, and cost-effective. This study evaluated the efficacy of enhancing Pleurotus citrinopileatus (PC) mushrooms’ vitamin D₂ content through pulsed ultraviolet (PUV) light and its impact on vitamin D status in humans. In a four-week randomized parallel trial, 36 healthy participants were assigned to three groups: a control group, a group consuming 10 g/day PUV-treated PC (PC-10 g), and a group consuming 100 g/day PUV-treated PC (PC-100 g). Blood samples collected pre- and post-intervention measured serum 25(OH)D₂, 25(OH)D₃, and biochemical parameters. After four weeks, serum 25(OH)D₂ levels significantly increased in the PC-10 g group (1.47 ± 1.42 ng/mL to 9.50 ± 7.10 ng/mL, p = 0.001) and in the PC-100 g group (1.94 ± 2.15 ng/mL to 21.82 ± 16.75 ng/mL, p = 0.002), showing a 10.2-fold rise. The PC-100 g group also experienced a 37.6% reduction in serum intact parathyroid hormone (I-PTH) levels (26.26 ± 9.84 pg/mL to 16.38 ± 5.53 pg/mL). No adverse effects were reported. PUV-treated PC mushrooms significantly increase serum 25(OH)D₂ levels and reduce I-PTH, particularly at higher doses. These findings underscore the potential of vitamin-D-enriched PC as a sustainable, fungi-derived food source for addressing vitamin D deficiency. Full article

Background/Objectives: Both hyperandrogenism (HA) and vitamin D deficiency (VDD) can separately lead to impaired vascular reactivity and ovulatory dysfunction in fertile females. The aim was to examine the early interactions of these states in a rat model of PCOS. Methods: Four-week-old adolescent female rats were divided into four groups: vitamin D (VD)-supplemented (n = 12); VD-supplemented and testosterone-treated (n = 12); VDD- (n = 11) and VDD-and-testosterone-treated (n = 11). Animals underwent transdermal testosterone treatment for 8 weeks. Target VD levels were achieved with oral VD supplementation and a VD-free diet. Estrous cycles were followed by vaginal smear, and quantitative histomorphometric measurements of the ovaries were also taken. In the 8th week, testosterone- and estrogen-induced relaxation of coronary arterioles was examined with pressure angiography. Estrogen receptor (ER) density and oxidative and nitrative stress parameters (Poly-(ADP-Ribose)-Polymerase and 3-nitrotyrosine) in the vessel wall were investigated with immunohistochemistry. Results: VDD caused impaired estrous cycles, and testosterone caused anovulatory cycles (the cycles were stopped at the diestrous phase). VDD combined with testosterone treatment resulted in reduced testosterone and estrogen vasorelaxation, lower ER density, and higher oxidative and nitrative stress in the vessel wall. Conclusions: PCOS with vitamin D deficiency may be associated with increased oxidative–nitrative stress in coronary arterioles. This oxidative and nitrative stress, potentially caused by hyperandrogenism and/or vitamin D deficiency, could impair estrogen-induced relaxation of the coronary arterioles, possibly by decreasing NO bioavailability and disrupting the estrogen-induced relaxation pathway. Full article