cholecalciferol and Polycystic-Ovary-Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It is characterized by hormonal, reproductive and metabolic disturbances, including hyperandrogenism, altered gonadotropin level, ovarian cysts and ovulatory dysfunction as well as insulin resistance, hyperinsulinemia and dyslipidemia. It was shown that increased insulin concentration is a plausible factor in the pathogenesis of PCOS. Insulin leads to overstimulation of ovarian theca cells to androgen biosynthesis and contributes to insulin resistance in tissues such as muscle, liver, adipose tissue and ovary of PCOS patients. Noteworthy, recent studies suggested that supplementation with vitamin D

Topics: Animals; Cholecalciferol; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome

Vitamin D3 is well-known as a major regulator of calcium and phosphorus homeostasis. A growing body of evidence highlights its crucial role in the regulation of reproductive processes in females. The role of vitamin D3 in the female reproductive tract has been extensively investigated because its receptor is abundant in reproductive organs, including ovary. Importantly, besides expression of vitamin D3 receptor, the ovary is an extrarenal site of vitamin D3 metabolism. The influence of vitamin D3 on follicular development and ovarian steroidogenesis has been investigated. Furthermore, vitamin D3 deficiency has also been associated with polycystic ovary syndrome, premature ovarian failure and ovarian cancer. The objective of this review is to summarize our knowledge about the contribution of vitamin D3 to physiological and pathological processes within the ovary.

Topics: Animals; Calcium; Cholecalciferol; Female; Humans; Ovary; Polycystic Ovary Syndrome; Receptors, Calcitriol; Vitamin D Deficiency

The objective of this study was to investigate the effect of vitamin D treatment on androgen levels and hirsutism scores in overweight women with PCOS.. A prospective, randomized, double-blind, placebo-controlled clinical study was conducted at King Abdullah University Hospital in Irbid, Jordan. Overweight Jordanian females aged 18-49 years with vitamin D deficiency and PCOS (n = 60) were assigned to two groups: the treatment group (n = 30) who received 50,000 IU per week of vitamin D. After receiving the treatment for 12 consecutive weeks, the levels of total testosterone, parathyroid hormone, free androgen index, and hirsutism score were significantly decreased (P < 0.001), and the levels of 25-hydroxyvitamin D (25(OH)D), sex hormone binding globulin, and phosphorus were significantly increased (P < 0.05). Furthermore, significant changes were observed in ovarian volume and follicle numbers and size ultrasonography, and in the regularity of the menstrual cycle (P < 0.001). In the placebo group, no significant changes were observed in either androgen levels, hirsutism score, or menstrual regularity.. Vitamin D. NCT02328404.

Topics: Adolescent; Adult; Androgens; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Hirsutism; Humans; Jordan; Middle Aged; Overweight; Parathyroid Hormone; Polycystic Ovary Syndrome; Prospective Studies; Testosterone; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Vitamin D status may be associated with insulin resistance and other key features of polycystic ovary syndrome (PCOS), but data from preliminary randomized controlled trials (RCTs) are conflicting. Therefore, we aimed to investigate the effects of vitamin D supplementation on plasma glucose area under the curve (AUCgluc, primary outcome measure) and on other metabolic and endocrine parameters (secondary outcome measures).. This study was a single-center, double-blind, randomized placebo-controlled trial conducted between December 2011 and July 2017 at the Medical University of Graz, Austria. One-hundred and eighty women with PCOS and 25-hydroxyvitamin D [25(OH)D] concentrations < 75 nmol/L were randomized in a 2:1 ratio to either receive 20,000 IU of cholecalciferol weekly or placebo over 24 weeks. Primary outcome was the between-group difference in AUCgluc at study end while adjusting for baseline values.. Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS with the exception of a reduced plasma glucose during OGTT.

Topics: Adult; Austria; Blood Glucose; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Vitamin D; Vitamins

There was inconsistent evidence about the benefit of vitamin D plus evening primrose oil (EPO) supplement intake on lipid profiles and reduced oxidative stress among women with polycystic ovary syndrome (PCOS). The current study was performed to evaluate the effects of vitamin D plus EPO supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D-deficient women with PCOS.. This randomized, double-blind, placebo-controlled trial was performed among 60 vitamin D-deficient women with PCOS. Participants were randomly assigned into two groups to receive either 1000 IU vitamin D3 plus 1000 mg EPO (n = 30) or placebo (n = 30) for 12 weeks. Metabolic profiles were quantified at baseline and after the 12-week intervention.. Compared with the placebo group, women in vitamin D and EPO co-supplementation group had significant increases in serum 25-hydroxyvitamin D (25(OH)D) (+10.7 ± 8.4 vs. -0.5 ± 1.6 ng/mL, p < 0.001) and plasma total glutathione (GSH) (+62.7 ± 58.0 vs. -0.7 ± 122.7 µmol/L, p = 0.01), while there were significant decreases in triglycerides (-7.3 ± 23.8 vs. +6.9 ± 26.3 mg/dL, p = 0.03), very low-density lipoprotein (VLDL) cholesterol levels (-1.5 ± 4.7 vs. +1.4 ± 5.3 mg/dL, p = 0.03), total/high-density lipoprotein cholesterol ratio (-0.3 ± 0.4 vs. -0.02 ± 0.4, p = 0.02), and malondialdehyde (MDA) concentration (-0.4 ± 0.4 vs. +0.5 ± 1.8 µmol/L, p = 0.008).. Overall, vitamin D and EPO co-supplementation for 12 weeks among vitamin D-deficient women with PCOS significantly improved triglycerides, VLDL cholesterol, GSH, and MDA levels.

Topics: Adult; Biomarkers; Cholecalciferol; Cholesterol, HDL; Cholesterol, VLDL; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; gamma-Linolenic Acid; Glutathione; Humans; Hypolipidemic Agents; Linoleic Acids; Malondialdehyde; Oenothera biennis; Outcome Assessment, Health Care; Oxidative Stress; Plant Oils; Polycystic Ovary Syndrome; Triglycerides; Vitamin D; Vitamin D Deficiency; Young Adult

Low plasma 25-hydroxy-vitamin D (25OHD) is associated with polycystic ovary syndrome (PCOS). Vitamin D deficiency may contribute to the development of insulin resistance, visceral fat and low level of adiponectin which are common feature in PCOS women. This study aimed to evaluate the effect of vitamin D supplementation on insulin resistance, visceral fat, and adiponectin in hypovitaminosis D women with polycystic ovary syndrome.. In this randomized, placebo-controlled clinical trial, 44 PCOS women aged 20-38 years with plasma 25OHD <20 ng/mL were randomized in the intervention or placebo groups and followed for 8 weeks. Participants received 50,000 IU of oral vitamin D3 once weekly in the intervention group or placebo. The visceral adipose tissue, Insulin resistance (HOMA-IR), HOMA-B, QUICKI, and circulating adiponectin were compared before and after the intervention within groups using paired tests and the mean changes were analyzed between two groups by independent t-test.. Of 44 eligible participates, 36 patients (81.8%) completed the study. After 8 week intervention, vitamin D supplementation compared to the placebo group significantly decreased fasting plasma glucose (FPG) (7.67 ± 7.66 versus 1.71 ± 7.50 mg/dL, p = .001) and significantly increased homeostasis model of assessment-estimated B cell function (HOMA-B) (129.76 ± 121.02 versus 48.32 ± 128.35, p = .014), Adiponectin (5.17 ± 8.09 versus -5.29 ± 8.64 mg/dL, p = .001), and serum vitamin D level (28.24 ± 6.47 versus 3.55 ± 4.25 ng/mL, p = .001).. Vitamin D supplementation in vitamin D deficient women with PCOS, improved the FPG, HOMA-B, Adiponectin, and serum vitamin D level.

Topics: Adiponectin; Adult; Blood Glucose; Cholecalciferol; Dietary Supplements; Female; Hormone Replacement Therapy; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Polycystic Ovary Syndrome; Treatment Outcome; Vitamin D Deficiency; Young Adult

There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis.. The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations.. This was a prospective, randomized, placebo-controlled trial.. The study was conducted at an academic-affiliated medical center.. Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015.. Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks.. Serum TGF-β1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment.. The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P < .01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80 ± 9 to 60 ± 6 d; P = .04), Ferriman-Gallwey score (9.8 ± 1.5 to 8.1 ± 1.5; P < .01), triglycerides (138 ± 22 to 117 ± 20 mg/dL; P = .03), and TGF-β1 to sENG ratio (6.7 ± 0.4 to 5.9 ± 0.4; P = .04). In addition, the ΔTGF-β1 to sENG ratio was positively correlated with Δtriglycerides (r = 0.59; P = .03).. VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-β1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-β drugs.

Topics: Adolescent; Adult; Antigens, CD; Biological Availability; Cholecalciferol; Dehydroepiandrosterone Sulfate; Endoglin; Female; Humans; Insulin Resistance; Lipids; Polycystic Ovary Syndrome; Prospective Studies; Receptors, Cell Surface; Socioeconomic Factors; Testosterone; Transforming Growth Factor beta1; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

To determine the effects of high-dose vitamin D on insulin sensitivity in polycystic ovary syndrome (PCOS).. Randomized, placebo-controlled trial.. Academic medical center.. Twenty-eight women with PCOS.. Vitamin D3, 12,000 IU, or placebo daily for 12 weeks.. The primary outcome was quantitative insulin sensitivity check index. Secondary outcomes included glucose and insulin levels during a 75-g oral glucose tolerance test and blood pressure.. Twenty-two women completed the study. Compared with placebo, vitamin D significantly increased 25-hydroxyvitamin D (mean [95% confidence interval] in vitamin D group 20.1 [15.7 to 24.5] ng/mL at baseline and 65.7 [52.3 to 79.2] ng/mL at 12 weeks; placebo 22.5 [18.1 to 26.8] ng/mL at baseline and 23.8 [10.4 to 37.2] ng/mL at 12 weeks). There were no significant differences in quantitative insulin sensitivity check index and other measures of insulin sensitivity; however, we observed trends toward lower 2-hour insulin and lower 2-hour glucose. We also observed a protective effect of vitamin D on blood pressure.. In women with PCOS, insulin sensitivity was unchanged with high-dose vitamin D, but there was a trend toward decreased 2-hour insulin and a protective effect on blood pressure.. NCT00907153.

Topics: Academic Medical Centers; Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Middle Aged; Pennsylvania; Pilot Projects; Polycystic Ovary Syndrome; Time Factors; Treatment Outcome; Vitamins; Young Adult

Insulin resistance is one of the most common features of polycystic ovary syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role in insulin resistance; thus, the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency. We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency. The current study was a randomized, placebo-controlled, double-blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26). The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone levels, as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D increased (6.9 ± 2.8 to 23.4 ± 6.1 ng/mL, P < .0001), and the parathyroid hormone level decreased (70.02 ± 43.04 to 50.33 ± 21.99 μ IU/mL, P = .02). There were no significant changes in the placebo group. There was a significant increase in insulin secretion in the vitamin D group (P = .01), but this was not significant compared with the placebo group. The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study. We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency.

Topics: Adult; Blood Glucose; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Parathyroid Hormone; Polycystic Ovary Syndrome; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS).. Single arm open label trial.. Twelve overweight and vitamin D deficient women with PCOS underwent a 2 hour oral glucose tolerance testing at baseline and following 3-month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530 mg elemental Ca daily.. Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted.. Improved serum 25OHD (p < 0.001) and reductions in total T (p = 0.036) and A (p = 0.090) levels were noted following 3-month supplementation, compared to baseline. Significant lowering in BP parameters was seen in participants with baseline BP ≥ 120/80 mmHg (n = 8) and in those with baseline serum 25OHD ≤20 ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05).. Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Calcifediol; Calcium, Dietary; Cholecalciferol; Cohort Studies; Dietary Supplements; Ergocalciferols; Female; Humans; Hyperandrogenism; Hypertension; Overweight; Patient Dropouts; Pilot Projects; Polycystic Ovary Syndrome; Testosterone Congeners; Vitamin D Deficiency; Young Adult

Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of insulin resistance. Hence, we aimed to examine the effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS women.. Fifty-seven PCOS women were included in the study. PCOS women received 20,000 IU cholecalciferol weekly for 24 weeks. Anthropometric measures, oral glucose tolerance test, and blood analyses of endocrine parameters were performed at baseline and after 12 weeks (V2) and 24 weeks (V3).. Forty-six PCOS women finished the study. 25-hydroxyvitamin D [25(OH)D] levels significantly increased from 28.0±11.0 ng/ml at baseline to 51.3±17.3 and 52.4±21.5 at V2 and V3, respectively (p<0.001). We observed a significant decrease of fasting and stimulated glucose (V3, p<0.05) and C-peptide levels (V2 and 3, p<0.001) after vitamin D treatment. Moreover, triglyceride and estradiol levels significantly decreased at V3 (p=0.001) and V2 (p=0.022), respectively, whereas total cholesterol (V2, p=0.008) and LDL cholesterol levels (V2, p=0.005; V3, p=0.026) significantly increased after vitamin D treatment. There were no changes in androgens. At V2, 14 out of 46 PCOS women previously affected by menstrual disturbances (30.4%) reported improvement of menstrual frequency; at V3, 23 out of 46 women (50.0%), who were oligo- or amenorrheic at baseline reported improvement.. Our results suggest that vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women. Further randomized controlled trails are warranted to confirm our findings.

Topics: Administration, Oral; Adolescent; Adult; Blood Glucose; C-Peptide; Cholecalciferol; Cholesterol; Cholesterol, LDL; Female; Humans; Menstruation; Menstruation Disturbances; Pilot Projects; Polycystic Ovary Syndrome; Prospective Studies; Vitamin D Deficiency

Polycystic ovary syndrome (PCOS) is an endocrine disorder with disrupted uterus structure and function. A positive effect of vitamin D. We analyzed the plasma levels and uterine transcript and protein expression of RARRES2 and ADIPOQ and their receptors (CCRL2, CMKLR1, GPR1, and ADIPOR1 and ADIPOR2, respectively) in rats with letrozole-induced PCOS.. In control animals, VD. our findings indicate a new mechanism of VD

Topics: Adipokines; Adiponectin; Animals; Cholecalciferol; Female; Humans; Polycystic Ovary Syndrome; Rats; Uterus

In this study, we investigated the effect of calcium and vitamin D (Ca/Vit D) supplementation on the clinical, hormonal, and metabolic profile of patients with low vitamin D levels. In addition, we investigated the effect of Ca/Vit D supplementation on asymmetric dimethylarginine (ADMA) level in patients with polycystic ovary syndrome (PCOS).. In total, 75 patients aged 19-35 years, with a normal body mass index and a diagnosis of PCOS and Vit D deficiency/insufficiency, were included in the study. Patients received 50,000 IU of vitamin D3 once a week for 8 weeks. Afterward, 2500 mg calcium carbonate equivalent to 1000 mg calcium ion and 9.68 mg cholecalciferol equivalent to 880 IU vitamin D3 were administered orally as a maintenance treatment once a day.. The mean age of the patients was 21.7 ± 3.5. After Ca/Vit D supplementation, Vit D levels significantly increased compared to baseline (8.6 ng/ml) levels. An increase in SHBG levels (p < 0.001), a decrease in total testosterone, FAI (p = 0.042), and ADMA levels (p < 0.001) were observed in the first and third months compared to the onset. Significant improvement compared to baseline was observed in menstrual irregularity and median mFG score.. Ca/Vit D supplementation can improve PCOS symptoms such as menstrual dysfunction, hirsutism, and hyperandrogenism. It may be effective in reducing the risk of cardiovascular disease in patients with PCOS later in life by decreasing ADMA levels, which is an indicator of endothelial dysfunction.

Topics: Calcium; Cholecalciferol; Dietary Supplements; Female; Humans; Metabolome; Polycystic Ovary Syndrome; Vitamin D; Vitamin D Deficiency

Assisted reproductive technologies (ART) are the main approach to restore fertility in patients with polycystic ovary syndrome (PCOS). The key milestones to achieve this result include the correct diagnosis, pre-pregnancy pre-treatment, pregnancy planning and the choice of infertility treatment.. The aim of this work was to evaluate the effect of a comprehensive method of pre-pregnancy pre-treatment which includes a vitamin complex with inositol and vitamin D3, on the levels of pituitary and ovarian hormones in women with infertility against the background of polycystic ovary syndrome.. The study involved 111 women with infertility and PCOS, who were offered different methods of pre-pregnancy pre-treatment prior to undergoing controlled ovarian stimulation according to a short protocol with recombinant gonadotropin corifollitropin alfa (Elonva®).. Our results indicate that in women with infertility against the background of PCOS the use of treatment which includes inositol at a dose of 2000 mg/day and vitamin D3 in an average prophylactic dose of 2 drops 2-3 times a day, depending on the concentration of 25(OH)D in blood serum, for 8 weeks, reduces the level of androgens and increases the level of oestrogen, suggesting normalisation of ovulation; while on the day of ovulation trigger the levels of oestradiol and progesterone were significantly lower (1.14 and 1.50 times, respectively) compared to a standard scheme of controlled ovarian stimulation with folic acid in pre-pregnancy pre-treatment.. These results indicate effectiveness of using a combination of a vitamin complex with inositol and vitamin D3 as a pre-pregnancy pre-treatment for the correction of endocrine and metabolic disorders in women with PCOS.

Topics: Cholecalciferol; Female; Humans; Infertility, Female; Inositol; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Vitamins

We examined the vasoactive effect of estradiol in a rat model of early PCOS and the influence of vitamin D deficiency (VDD). We created a model of chronic hyperandrogenism and VDD in adolescent female Wistar rats (N = 46) with four experimental groups: vitamin D supplemented (T-D+), VDD (T-D-), hyperandrogenic and vitamin D supplemented (T+D+), and hyperandrogenic and VDD (T+D-). T+ groups received an 8-week-long transdermal Androgel treatment, D-animals were on vitamin D-reduced diet and D+ rats were supplemented orally with vitamin D3. Estrogen-induced vasorelaxation of thoracic aorta segments were measured with a wire myograph system with or without the inhibition of endothelial nitric oxide synthase (eNOS) or cyclooxygenase-2 (COX-2). The distribution of estrogen receptor (ER), eNOS and COX-2 in the aortic wall was assessed by immunohistochemistry. VDD aortas showed significantly lower estradiol-induced relaxation independently of androgenic status that was further decreased by COX-2 inhibition. COX-2 inhibition failed to alter vessel function in D+ rats. Inhibition of eNOS abolished the estradiol-induced relaxation in all groups. Changes in vascular function in VDD were accompanied by significantly decreased ER and eNOS staining. Short-term chronic hyperandrogenism failed to, but VDD induced vascular dysfunction, compromised estrogen-dependent vasodilatation and changes in ER and eNOS immunostaining.

Topics: Animals; Aorta; Cholecalciferol; Disease Models, Animal; Estradiol; Estrogens; Female; Nitric Oxide Synthase Type III; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Vasodilation; Vitamin D Deficiency; Vitamins

Vitamin D

Topics: Adipose Tissue; Administration, Oral; Animals; Calcitriol; Cholecalciferol; Female; Letrozole; Ovary; Polycystic Ovary Syndrome; Rats; Rats, Wistar

Polycystic ovarian syndrome (PCOS) is a disorder characterized by oligomenorrhea, anovulation, and hyperandrogenism. Altered mitochondrial biogenesis can result in hyperandrogenism. The goal of this study was to examine the effect of vitamin D3 on mitochondrial biogenesis of the granulosa cells in the PCOS-induced mouse model. Vitamin D3 applies its effect via the mitogen-activated pathway kinase-extracellular signal-regulated kinases (MAPK-ERK1/2) pathway. The PCOS mouse model was induced by the injection of dehydroepiandrosterone (DHEA). Isolated granulosa cells were subsequently treated with vitamin D3, MAPK activator, and MAPK inhibitor. Gene expression levels were measured using real-time polymerase chain reaction. MAPK proteins were investigated by western blot analysis. We also determined reactive oxygen species (ROS) levels with 2', 7'-dichlorofluorescein diacetate. Mitochondrial membrane potential (mtMP) was also measured by TMJC1. Mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-α and nuclear respiratory factor), antioxidant (superoxide dismutase, glutathione peroxidase, and catalase), and antiapoptotic (B-cell lymphoma-2) genes were upregulated in the PCOS mice that treated with vitamin D3 compared with the PCOS mice without any treatment. Vitamin D3 and MAPK activator-treated groups also reduced ROS levels compared with the nontreated PCOS group. In summary, vitamin D3 and MAPK activator increased the levels of mitochondrial biogenesis, MAPK pathway, and mtMP markers, while concomitantly decreased ROS levels in granulosa cells of the PCOS-induced mice. This study suggests that vitamin D3 may improve mitochondrial biogenesis through stimulation of the MAPK pathway in cultured granulosa cells of DHEA-induced PCOS mice which yet to be investigated.

Topics: Animals; Apoptosis; Catalase; Cholecalciferol; Dehydroepiandrosterone; Disease Models, Animal; Female; Glutathione Peroxidase; Granulosa Cells; Humans; MAP Kinase Signaling System; Mice; Nuclear Respiratory Factors; Organelle Biogenesis; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Polycystic Ovary Syndrome; Reactive Oxygen Species; Superoxide Dismutase

The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients.. Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load.. After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group.. Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS.

Topics: Adolescent; Adult; Androstenedione; Blood Glucose; Body Mass Index; Cholecalciferol; Dietary Supplements; Female; Humans; Insulin Resistance; Polycystic Ovary Syndrome; Prospective Studies; Testosterone; Vitamin D; Vitamin D Deficiency; Young Adult

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in reproductive-aged women. Hormonal abnormality caused by steroidogenesis disturbances appears to be the main culprit of the clinical picture in PCOS. Vitamin D3 could regulate steroidogenesis in granulosa cells, but the mechanism of action of vitamin D3 on steroidogenesis remains unknown. AMP-activated protein kinase (AMPK) has a modulating role in steroid hormone production. We investigated the effect of vitamin D3 on steroidogenesis in cultured granulosa cells of dehydroepiandrosterone-induced PCOS mice and studied the involvement of AMPK signalling pathway in the current process. Immunoblotting assay showed that vitamin D3 could increase phosphorylation of AMPK alpha and acetyl-CoA carboxylase, main substrate of AMPK. Vitamin D3 and 5-aminoimidazole-4-carboxamide-1-β-D-riboside or Aicar (AMPK activator) not only reduced gene expression of steroidogenic enzymes (P450scc or Cyp11a1, StAR, Cyp19a1 and 3B-HSD), but also reduced production of progesterone and 17B-estradiol assessed by radioimmunoassay. Pretreatment with compound C (AMPK inhibitor) decreased APMK phosphorylation and eliminated the effects of vitamin D3 and Aicar on steroidogenic enzymes expression and estradiol and progesterone production. This study showed that vitamin D3 has the main role in regulating of steroidogenesis in granulosa cells of mouse polycystic ovary through activation of the AMPK signalling pathway.. Polycystic ovarian syndrome (PCOS) is an endocrine disorder of women in reproductive age. This disorder is partly related to disruption in steroidogenesis pathway and dysregulation of estradiol and progesterone production in granulosa cells of polycystic ovaries. Previously, we have shown that vitamin D3 could modulate steroidogenesis pathway in PCOS granulosa cells. In this study, we investigate the molecular mechanism of vitamin D3 in regulation of steroidogenesis pathway. We have shown that vitamin D3 has a modulating role in steroidogenesis pathway of granulosa cells by regulation of AMP-activated protein kinase (AMPK) as an underlying molecular mechanism in mouse polycystic ovary.

Topics: AMP-Activated Protein Kinases; Animals; Cells, Cultured; Cholecalciferol; Dehydroepiandrosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Activation; Female; Granulosa Cells; Mice; Mice, Inbred BALB C; Polycystic Ovary Syndrome; Steroids; Structure-Activity Relationship

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes including Cyp11a1, StAR, Cyp19a1, and 3β-HSD were upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3β-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS.. AMHR-II: anti-müllerian hormone receptor-II; 3β-HSD: 3β-hydroxysteroid dehydrogenase; Cyp11a1: Cytochrome P450 Family 11 Subfamily A Member 1; Cyp19a1: cytochrome P450 aromatase; DHEA: dehydroepiandrosterone; FSH: follicle stimulating hormone; FSHR: follicle stimulating hormone receptor; IVF: in vitro fertilization; 25OHD: 25-hydroxy vitamin D; OHSS: ovarian hyperstimulation syndrome; PCOS: polycystic ovarian syndrome; P450scc: P450 side-chain cleavage enzyme; StAR: steroidogenic acute regulatory protein; VDRs: vitamin D receptors.

Topics: Animals; Cholecalciferol; Disease Models, Animal; Drug Evaluation, Preclinical; Estrous Cycle; Female; Gonadal Steroid Hormones; Granulosa Cells; Mice, Inbred BALB C; Ovary; Polycystic Ovary Syndrome

Low vitamin D serum level has been reported in women with polycystic ovary syndrome (PCOS) compared to controls. A few in vitro studies showed that the bioactive form of vitamin D is able to modulate the expression of the anti-Müllerian hormone (AMH) gene. However, in vivo studies failed to demonstrate clearly whether low vitamin D3 serum level is involved in the AMH excess of PCOS. This prospective study evaluates serum vitamin D3 and AMH levels in women with PCOS and in controls, before and after vitamin D supplementation.. Among vitamin D deficient patients, 23 patients with PCOS were compared to 27 women with normal ovarian reserve (NOR). The vitamin D deficient patients received a vitamin D supplementation according to the depth of their insufficiency. For the 23 patients with PCOS and the 27 controls, serum AMH assay and serum calciotropic hormone assays [25-hydroxyvitamin D (25[OH]D), 1,25 dihydroxyvitamin D (1,25[OH]. Serum 25(OH)D levels before treatment were statistically lower in PCOS women than in NOR patients (P<0.05), even after adjustment for BMI, age and AMH level, but not after adjustment for waist circumference measurement. No difference in the serum AMH levels before and after treatment was observed neither in PCOS patients nor in NOR patients. In both groups, 25(OH)D serum levels were not related to serum AMH levels, serum 1,25(OH). We found no evidence that serum calciotropic hormones are linked to circulating AMH levels, particularly in PCOS.

Topics: Adolescent; Adult; Anti-Mullerian Hormone; Case-Control Studies; Cholecalciferol; Female; Humans; Polycystic Ovary Syndrome; Vitamin D Deficiency; Waist Circumference; Young Adult

Topics: Cholecalciferol; Depression; Dietary Supplements; Female; Humans; Polycystic Ovary Syndrome; Treatment Outcome; Vitamin D Deficiency; Vitamins

Polycystic ovary syndrome (PCOS) causes vascular damage to arteries; however, there are no data for its effect on veins. Our aim was to clarify the effects of dihydrotestosterone (DHT)-induced PCOS both on venous biomechanics and on pharmacological reactivity in a rat model and to test the possible modulatory role of vitamin D3 (vitD). PCOS was induced in female Wistar rats by DHT treatment (83 μg/day, subcutaneous pellet). After 10 wk, the venous biomechanics, norepinephrine (NE)-induced contractility, and acetylcholine-induced relaxation were tested in saphenous veins from control animals and from animals treated with DHT or DHT with vitD using pressure angiography. Additionally, the expression levels of endothelial nitric oxide synthase (eNOS) and cyclooxygenase (COX-2) were measured using immunohistochemistry. Increased diameter, wall thickness, and distensibility as well as decreased vasoconstriction were detected after the DHT treatment. Concomitant vitD treatment lowered the mechanical load on the veins, reduced distensibility, and resulted in vessels that were more relaxed. Although there was no difference in the endothelial dilation tested using acetylcholine (ACh), the blocking effect of N(G)-nitro-l-arginine methyl ester (l-NAME) was lower and was accompanied by lower COX-2 expression in the endothelium after the DHT treatment. Supplementation with vitD prevented these alterations. eNOS expression did not differ among the three groups. We conclude that the hyperandrogenic state resulted in thicker vein walls. These veins showed early remodeling and altered vasorelaxant mechanisms similar to those of varicose veins. Alterations caused by the chronic DHT treatment were prevented partially by concomitant vitD administration.

Topics: Animals; Cholecalciferol; Cyclooxygenase 2; Dihydrotestosterone; Disease Models, Animal; Female; Lower Extremity; Nitric Oxide Synthase Type III; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Saphenous Vein; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Venous Pressure

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

Topics: Animals; Aorta; Cholecalciferol; Endothelium, Vascular; Estradiol; Estrogens; Female; Muscle, Smooth, Vascular; Poly Adenosine Diphosphate Ribose; Poly(ADP-ribose) Polymerases; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Vasoconstriction; Vasodilation; Vitamins

In polycystic ovary syndrome (PCOS), metabolic and cardiovascular dysfunction is related to hyperandrogenic status and insulin resistance, however, Vitamin D3 has a beneficial effect partly due to its anti-oxidant capacity. Nitrative stress is a major factor in the development of cardiovascular dysfunction and insulin resistance in various diseases. Our aim was to determine the effects of vitamin D3 in a rat model of PCOS, particularly the pathogenic role of nitrative stress.. Female Wistar rats weighing 100-140g were administered vehicle (C), dihydrotestosterone (DHT) or dihydrotestosterone plus vitamin D3 (DHT+D) (n=10 per group). On the 10th week, acetylcholine (Ach) induced relaxation ability of the isolated thoracic aorta rings was determined. In order to examine the possible role of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) pathways in the impaired endothelial function, immunohistochemical labeling of aortas with anti-eNOS and anti-COX-2 antibodies was performed. Leukocyte smears, aorta and ovary tissue sections were also immunostained with anti-nitrotyrosine antibody to determine nitrative stress.. Relaxation ability of aorta was reduced in group DHT, and vitamin D3 partly restored Ach induced relaxation. eNOS labeling was significantly lower in DHT rats compared to the other two groups, however COX-2 staining showed an increment. Nitrative stress showed a significant increase in response to dihydrotestosterone, while vitamin D3 treatment, in case of the ovaries, was able to reverse this effect.. Nitrative stress may play a role in the pathogenesis of PCOS and in the development of the therapeutic effect of vitamin D3.

Topics: Animals; Aorta, Thoracic; Cholecalciferol; Cyclooxygenase 2; Endothelium, Vascular; Female; Humans; Nitric Oxide Synthase Type III; Ovary; Oxidative Stress; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Vasodilation; Vitamins

Topics: Adolescent; Adult; Case-Control Studies; Cholecalciferol; Cross-Sectional Studies; Female; Humans; India; Metabolic Syndrome; Polycystic Ovary Syndrome; Vitamin D Deficiency; Young Adult

To investigate the vascular dysfunction caused by insulin resistance in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an animal model.. Controlled experimental animal study.. Animal laboratory at a university research institute.. Thirty female Wistar rats.. Rats were divided into groups at age 21-28 weeks. Twenty of them were subjected to dihydrotestosterone (DHT) treatment (83 μg/d); ten of them also received parallel vitamin D treatment (120 ng/100 g/wk). Oral glucose tolerance tests with insulin level measurements were performed. Gracilis arterioles were tested for their contractility as well as their nitric oxide (NO)-dependent and insulin-induced dilation using pressure arteriography.. Several physiologic parameters, glucose metabolism, and pressure arteriography.. DHT treatment increased the passive diameter of resistance arterioles, lowered norepinephrine-induced contraction (30.1 ± 4.7% vs. 8.7 ± 3.6%) and reduced acetylcholine-induced (122.0 ± 2.9% vs. 48.0 ± 1.4%) and insulin-induced (at 30 mU/mL: 21.7 ± 5.3 vs. 9.8 ± 5.6%) dilation. Vitamin D treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation.. In DHT-treated rats, in addition to metabolically proven insulin resistance, decreased insulin-induced vasorelaxation was observed and was improved by vitamin D treatment without affecting NO-dependent relaxation. The reduction in insulin-induced dilation of arterioles is an important as yet undescribed pathway of vascular damage in PCOS and might explain the clinical effectiveness of vitamin D treatment.

Topics: Acetylcholine; Animals; Arterioles; Blood Glucose; Cholecalciferol; Dihydrotestosterone; Disease Models, Animal; Enzyme Inhibitors; Female; Glucose Tolerance Test; Insulin; Insulin Resistance; Muscle, Skeletal; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Vasodilation; Vasodilator Agents

The aim of this study was to clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) on pharmacological reactivity of a resistance vessel in a rat model and the possible modulatory role of 1,25-(OH)₂-cholecalciferol (vitamin D₃). The PCOS model was induced in adolescent female Wistar rats by a 10-week DHT treatment. Norepinephrine induced contractility and acetylcholine relaxation were tested in arterioles by pressure arteriography in control as well as DHT- and DHT plus vitamin D₃-treated (DHT+D3) animals. Decreased vasoconstriction and dilatation were detected after DHT treatment. Concomitant vitamin D₃ treatment increased the contractile response and resulted in more relaxed vessels. Endothelial dilation tested with acetylcholine was lower after DHT treatment, this effect was not depend on vitamin D₃ supplementation. In conclusion, hyperandrogenic state resulted in reduced endothelium- and smooth muscle-dependent vasorelaxation and constriction with a complete loss of nitric oxide (NO)-dependent relaxation compared with controls. These alterations caused by chronic DHT treatment were partially reversed by concomitant vitamin D₃ administration.

Topics: Animals; Arterioles; Cardiovascular Agents; Cardiovascular Diseases; Cholecalciferol; Dihydrotestosterone; Disease Models, Animal; Drug Implants; Endothelium, Vascular; Female; Injections, Subcutaneous; Muscle, Skeletal; Muscle, Smooth, Vascular; Polycystic Ovary Syndrome; Rats; Rats, Wistar; Thigh; Vascular Resistance; Vasoconstriction; Vasodilation

To clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) on arteriolar biomechanics in a rat model and the possible modulatory role of vitamin D3.. The PCOS model was induced in female Wistar rats by ten-weeks DHT treatment. Arteriolar biomechanics was tested in arterioles by pressure arteriography in control as well as DHT- and DHT with vitamin D3-treated animals in contracted and passive conditions. Increased wall stress and distensibility as well as increased vascular lumen were detected after DHT treatment. Concomitant vitamin D3 treatment lowered the mechanical load of the arterioles and restored the vascular diameter.. The hyperandrogenic state resulted in more rigid, less flexible arteriolar walls with increased vascular lumen compared with controls. DHT treatment caused eutrophic remodelling of gracilis arteriole. These prehypertensive alterations caused by chronic DHT treatment were mostly reversed by concomitant vitamin D3 administration.

Topics: Adaptation, Physiological; Animals; Arterioles; Biomechanical Phenomena; Cholecalciferol; Disease Models, Animal; Elasticity; Female; Muscle, Skeletal; Polycystic Ovary Syndrome; Prehypertension; Rats; Rats, Wistar; Stress, Mechanical; Vitamins