SEARCH · PubMed Health

Results for “PCOS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2025

Genomic relationship between polycystic ovary syndrome and bipolar disorder.

Women with bipolar disorder (BIP) have a higher risk of developing polycystic ovary syndrome (PCOS). Shared genetic architecture may underlie this comorbidity. Valproate, a mood-stabilizer commonly used to treat BIP, increases the risk of PCOS. Still, the mechanism underlying PCOS in BIP remains unknown. Here, we aimed to identify genetic variants shared between BIP and PCOS, as well as their interaction with valproate. We used the results of large-scale genome-wide association studies of BIP (41,510 cases and 354,340 controls), and PCOS (3,609 cases and 229,788 controls). Using conditional false discovery rate, we discovered genetic variants jointly associated with BIP and PCOS. Gene mapping of identified variants was performed using the Open Targets platforms. We analyzed the tissue-specific expression, interaction with valproate, and involvement in biological pathways of the mapped genes. We identified two loci shared between BIP and PCOS. Among the 10 genes mapped to the locus on chromosome 8:11455262, GATA4, NEIL2, and FDFT1 showed expression profiles suggesting their role in the observed comorbidity. Mapped to the locus on chromosome 12:2499849, CACNA1C, FKBP4, DCP1B, and ITFG2 are expressed in both the ovaries and the brain. CACNA1C expression is affected by valproate, and CACNA1C plays a role in biological pathways involving other valproate-affected genes. We identified shared genetic underpinnings of BIP and PCOS, and implicated genes which may explain the biological mechanisms of the comorbidity between these disorders and a potential mechanism for the role of valproate.

bipolar disorder↗

PubMed2024

Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis. OBJECTIVE: This work aimed to group PCOS GWAS loci into genetic clusters associated with disease pathophysiology. METHODS: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N = 62 252). Associations with clinical outcomes (type 2 diabetes [T2D], coronary artery disease [CAD], and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N = 898,130, CARDIOGRAM/UKBB, N = 547 261) and individual-level pPS in MGBB. RESULTS: Four PCOS genetic clusters were identified with top loci indicated as following: (i) cluster 1/obesity/insulin resistance (FTO); (ii) cluster 2/hormonal/menstrual cycle changes (FSHB); (iii) cluster 3/blood markers/inflammation (ATXN2/SH2B3); (iv) cluster 4/metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (P = 6.6 × 10-29); cluster 2 with increased age of menarche (P = 1.5 × 10-4); cluster 3 with multiple decreased blood markers, including mean platelet volume (P = 3.1 ×10-5); and cluster 4 with increased alkaline phosphatase (P = .007). PCOS genetic clusters GWAS-pPSs were also associated with disease outcomes: cluster 1 pPS with increased T2D (odds ratio [OR] 1.07; P = 7.3 × 10-50), with replication in MGBB all participants (OR 1.09, P = 2.7 × 10-7) and females only (OR 1.11, 4.8 × 10-5). CONCLUSION: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes.

Humans↗

PubMed2026

Multitarget interactions of bisphenol A in polycystic ovary syndrome: evidence from integrated network toxicology, mendelian randomization, and molecular docking.

OBJECTIVE: To study the potential pathogenic mechanisms of bisphenol A (BPA) in polycystic ovary syndrome (PCOS) using an integrative computational strategy. DESIGN: Integrative computational study combining network toxicology, Mendelian randomization (MR), and molecular docking. SUBJECTS: For MR analysis, genetic data were sourced from large European-ancestry cohorts, including plasma protein quantitative trait loci data and genome-wide association study summary statistics for PCOS (3,045 cases and 267,780 controls). EXPOSURE: In silico exposure to BPA for target prediction; genetically predicted plasma protein levels for causal inference. MAIN OUTCOME MEASURES: Identification of overlapping targets between BPA and PCOS; functional enrichment pathways; causal effects of prioritized proteins on PCOS risk (odds ratios with 95% confidence intervals); binding affinities between BPA and core targets (kcal/mol). RESULTS: Network toxicology identified 310 overlapping targets between BPA and PCOS. Enrichment analyses revealed significant involvement in endocrine signaling, inflammatory pathways (eg, IL-17), and cellular processes. MR demonstrated that genetically elevated levels of RET, CXCL8, HTR6, MMP1, MMP9, NTRK1, and TNNI2 were significantly associated with increased PCOS risk, whereas higher PSAP and SHBG levels were protective. Molecular docking confirmed stable binding between BPA and all nine key targets, with strongest affinity for SHBG (-8.4 kcal/mol), followed by NTRK1, TNNI2, and RET. CONCLUSION: This integrative investigation suggests that BPA may contribute to PCOS pathogenesis through multitarget interactions involving inflammatory mediators, endocrine regulators, and tissue remodeling proteins. The findings provide prioritized targets and mechanistic insights for future experimental validation and environmental risk assessment.

Female↗

PubMed2026

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

Humans↗

PubMed1992

Impaired glucose effectiveness in patients with polycystic ovary syndrome.

Insulin resistance and glucose intolerance are common features of polycystic ovary syndrome (PCOS). We have investigated the effect of glucose on the fractional glucose disappearance in patients with PCOS and in age- and weight-matched control subjects. The minimal model method as applied to a frequently sampled intravenous glucose tolerance test was employed. The insulin sensitivity index (Si) and glucose effectiveness (SG) were calculated with the MINMOD program. Testosterone, androstenedione and free testosterone concentrations were significantly higher in PCOS subjects. Glucose-induced glucose clearance (SG) and insulin sensitivity were significantly lower in PCOS subjects than controls [SG: 2.7 +/- 0.3 versus 1.8 +/- 0.1 x 100/min; P less than 0.01; Si: 133.4 +/- 20.0 versus 65.6 +/- 6.4/min (nmol/ml)]. Six PCOS women had an SG value within the normal range (greater than 2.0 x 100/min) but had a similar Si to that found in PCOS women with abnormal SG. We suggest that independent alterations in both glucose- and insulin-mediated glucose uptake occur in patients with PCOS. The underlying disturbance in glucose effectiveness may be similar to that found in familial non-insulin dependent diabetes mellitus.

Adult↗

PubMed1992

Follicular fluid insulin-like growth factor binding protein profiles in polycystic ovary syndrome.

Insulin-like growth factor binding proteins (IGFBPs) are believed to modulate the actions of IGF-I and IGF-II at the cellular level. We have examined, by Western ligand blot analysis, the IGFBP profiles in follicular fluid (FF) from patients with polycystic ovarian syndrome (a disorder of ovarian folliculogenesis), compared to FF from atretic and developing (estrogenic) follicles from normally cycling women. IGFBPs with apparent mol wts (Mr) of 41.5, 38.5, 31, 28, and 24kDa were detected in PCOS FF. The profile of IGFBPs in PCOS FF was indistinguishable from that seen in atretic follicles in cycling women. However, higher levels of the 31, 28, and 24kDa IGFBPs were observed in PCOS FF, compared to healthy, estrogenic follicles. Using specific antisera, the 41.5 and 38.5kDa IGFBPs were identified as IGFBP-3, and the 31kDa IGFBP as IGFBP-2. IGFBP-1, however, was not appreciably detectable in PCOS FF, by Western ligand blotting. Endoglycosidase F treatment of FF decreased the Mr of the 28kDa IGFBP to 24kDa, and neither the 28kDa nor the 24kDa IGFBP was immunoprecipitated by antibodies to IGFBP-1, -2, or -3. Elevated levels of 28kDa and 24kDa IGFBPs in PCOS FF may represent glycosylated and core forms of IGFBP-4. The data presented herein show that in PCOS FF, as well as in FF from atretic follicles from normally cycling women, IGFBP-2 and 28 and 24kDa IGFBPs are present in greater amounts, compared to levels in FF from healthy, developing, estrogenic follicles. One or more of the IGFBP species elevated in atretic and PCOS follicles may bind IGFs in FF, thereby inhibiting IGF action on the granulosa during normal folliculogenesis.

Blotting, Western↗

PubMed2026

Evaluation of metabolic, reproductive, and gut microbiota alterations in a comparative study of different preclinical models of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifaceted, complex metabolic and endocrine disease where gut flora is considered an important factor in causing PCOS. This study aimed to identify a suitable PCOS model that contributes to gut microbial dysbiosis and metabolic and hormonal disturbances. Prepubertal SD rats were administered with normal control (NC), dihydrotestosterone (DHT), DHT with fructose (F), DHT+ high fat diet (HFD) for 91 days, dehydroepiandrosterone (DHEA), DHEA with fructose, DHEA with HFD for 30 days, sodium valproate (SV), sodium valproate with fructose, and sodium valproate with HFD for 21 days. The estrous cycles were assessed over this timeframe. At the end of the experiment, superoxide dismutase and uterine and ovarian morphology were evaluated, along with hormone levels, lipid profiles, and 16S rRNA genomic sequencing. All models exhibited PCOS characteristics, including hormonal imbalances, insulin resistance (p ≤ .001), multiple follicular cysts on ultrasonography, and histological alterations. Gut microbial dysbiosis was observed across all PCOS-induced groups; however, the DHT alone group showed more pronounced alterations in microbial composition than the other experimental groups. Specifically, the DHT alone group exhibited reduced abundance of Firmicutes and increased abundance of Proteobacteria. Among the evaluated models, the DHT-only model showed more pronounced metabolic, hormonal, reproductive, and gut microbial alterations and may serve as a suitable model for PCOS research.

Animals↗

PubMed2026

Single-cell expression quantitative trait locus Mendelian randomization reveals immune cell-specific causal regulatory networks and actionable targets in polycystic ovary syndrome.

ObjectiveTo systematically investigate whether the pathogenesis of polycystic ovary syndrome (PCOS) is causally related to dysregulated gene expression in specific immune cell subsets, and to evaluate the potential of these causal genes as actionable drug targets.MethodsThis study employed a two-sample Mendelian randomization (MR) framework using publicly available genome-wide association study (GWAS) summary statistics. The participant data included 797 PCOS cases and 140,558 controls (no direct patient recruitment was involved). Instrumental variables were derived from high-resolution immune cell-specific single-cell expression quantitative trait locus (sc-eQTL) data (OneK1K project) across 14 immune cell types. Primary analyses utilized the inverse-variance weighted (IVW) method. Shared causal variants were validated using Bayesian colocalization. Phenome-wide association analysis (PheWAS), external transcriptomic dataset validation (GSE8157), and DrugBank database screening were conducted for pleiotropy assessment and drug repositioning.ResultsMR analysis revealed genome-wide significant causal associations for GLIPR1 in non-classical monocytes (Mono NC) and XBP1 in CD4+ effector memory T cells (CD4 ET) with PCOS risk. Higher GLIPR1 expression was associated with a decreased PCOS risk (OR = 0.669, P = 4.34×10-6), whereas higher XBP1 expression was associated with an increased risk (OR = 1.406, P = 9.53×10-8). Colocalization analysis confirmed that GLIPR1 shares a causal variant with PCOS (PP.H4 = 96.73%). PheWAS and external validation confirmed the safety profile and significant upregulation (P = 0.03) of GLIPR1. Drug repositioning identified SOT-107, a Phase III protein therapy drug, as a potential interacting agent for GLIPR1.ConclusionsThis sc-eQTL MR study reveals immune cell-specific causal regulatory networks in PCOS. GLIPR1 in non-classical monocytes represents a high-confidence protective target, while XBP1 provides suggestive evidence for immune-mediated pathogenesis. The candidate drug SOT-107 highlights theoretical repositioning opportunities, though rigorous preclinical validation remains required.

Female↗

PubMed2025

Association of CYP19 gene SNPs (rs7176005 and rs6493497) with polycystic ovary syndrome susceptibility in Northern Chinese women.

PURPOSE: The objective of this study was to elucidate the relationship between two single nucleotide polymorphisms (SNPs) rs7176005 and rs6493497 in CYP19 gene and the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women. METHODS: In this case-control study, a total of 340 women with PCOS and 340 matched healthy controls were recruited. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to investigate two SNPs (rs7176005 and rs6493497) in the 5'-flanking region of CYP19 gene exon 1. RESULTS: We observed a significant association of rs7176005 and rs6493497 with reduced risk of PCOS. Compared with CC genotype, a significant association of CT genotype (p = 0.019), TT genotype (p < 0.001) and combined CT + TT genotype (p < 0.001) with reduced risk of PCOS was observed. The result of linkage disequilibrium analysis showed that these two SNPs are in complete linkage disequilibrium (r2 = 1). For rs7176005 SNP, compared with CC genotype, CT, TT and CT + TT genotypes reduced the risk of PCOS. The age, BMI-adjusted OR were 0.650 (95% CI = 0.460-0.917), 0.158 (95% CI = 0.066-0.376) and 0.545(95% CI = 0.391-0.759), respectively. CONCLUSIONS: These findings highlight a significant association between CYP19 gene polymorphisms and PCOS susceptibility, implying potential protective effects of T and A alleles. Of course, the major limitation of this study is the sample size of the case-control study. Larger cohort studies are needed to confirm these findings and investigate the underlying causes.

Adult↗

PubMed1992

Variability of serum gonadotropin and dehydroepiandrosterone sulfate concentrations in women with polycystic ovary syndrome.

This study was designed to assess the variability of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandrosterone sulfate (DHEAS) levels over time in women with polycystic ovary syndrome (PCOS). Serum LH, FHS and DHEAS concentrations were determined for four consecutive monthly intervals in three groups of women: group 1, normal cycling women in the follicular phase (n = 9); group 2, normal cycling women in the luteal phase (n = 10); and group 3, women with PCOS (n = 11). For LH, DHEAS and the LH/FSH ratio, a histogram was constructed based on whether the subjects in each group had 0, 1, 2, 3 or 4 high values. In addition, the coefficient of variation (CV) for the four individual values of each hormone was determined for each subject to quantitatively assess the variability of measurement over time. Histographic analysis revealed that an elevated LH value or an elevated LH/FSH ratio in PCOS was inconsistent. For DHEAS, 9 of 11 PCOS subjects had either 0 (n = 7) or 4 (n = 2) high values, suggesting that such determinations are relatively consistent. We conclude that (1) isolated LH or LH/FSH measurements may not be sufficiently reproducible to be clinically useful despite evidence that LH values may be more stable in PCOS than in normal women and (2) a normal or high DHEAS value in PCOS is more likely to be consistently replicated, although the number of subjects studied limits the power of this conclusion.

Adult↗

PubMed1992

Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis.

OBJECTIVES: To provide an up-to-date review of studies that have examined the physiological effects of insulin and insulin-like growth factor I (IGF-I) on ovarian growth, maturation, and steroid synthesis, their physiological role in puberty, and their pathophysiological role in polycystic ovarian syndrome (PCOS). To deduce from these data a hypothesis, explaining the pathogenetic connections between puberty and PCOS. DATA IDENTIFICATION: The most relevant studies related to this topic have been identified through a computerized bibliographic search (MEDLINE) and through manual scanning of what has been published during recent years in the most important journals in the field of reproductive endocrinology. RESULTS: Insulin and IGF-I stimulate ovarian growth and potentiate the actions of gonadotropins on ovarian steroid synthesis. Insulin also augments the bioactive concentrations of IGF-I and androgens through regulation of the synthesis of their respective binding proteins insulin-like growth factor-1 binding protein (IGFBP-1) and sex hormone-binding globulin (SHBG) in the liver. Insulin and IGF-I might also be able to increase the adrenal sensitivity to adrenocorticotropic hormone (ACTH). Insulin resistance with compensating hyperinsulinism is a common feature of PCOS. It is also a normal phenomenon during puberty. Polycystic ovarian syndrome often develops during puberty. Ultrasonographic investigations suggest that it is much more common during adolescence than generally assumed. Actually, there is a striking resemblance between the endocrine characteristics of puberty and some forms of PCOS. Both conditions are characterized by insulin resistance, hyperpulsatile gonadotropin secretion, hyperactive ovarian and adrenal androgen synthesis, and decreased levels of IGFBP-1 and SHBG. CONCLUSION: We propose the progressively increasing insulin levels and IGF-I activity during puberty as inducing factors in the development of PCOS in susceptible subjects.

Female↗

PubMed2026

Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Humans↗

PubMed2026

Metabolic Stress Testing Reveals Persistent Lipid-Handling Dysfunction in Women With Polycystic Ovary Syndrome Despite Exercise Training.

AIM: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and metabolic dysfunction, yet baseline metabolomic studies show inconsistent findings. We investigated whether metabolic abnormalities in PCOS emerge under physiological stress and how these responses are modified by exercise training. MATERIALS AND METHODS: Twelve women with PCOS and 10 controls completed hyperinsulinaemic-euglycaemic clamps with randomised saline or lipid infusion, before and after 8 weeks of supervised exercise. Plasma metabolomics (163 metabolites) were measured at baseline, post-infusion and post-clamp. Linear mixed-effects models assessed Group × Timepoint × Intervention interactions. RESULTS: No baseline metabolite differences were observed between groups. A significant three-way interaction (p = 0.008) indicated condition-dependent trajectory divergence. Post hoc analysis revealed a specific divergence during post-exercise lipid challenge (p = 0.048). Women with PCOS showed reduced suppression of ether-linked phosphatidylcholines during insulin-stimulated lipid loading (PC ae C44:4, p = 0.031), despite exercise-induced improvements in fitness and normalisation of amino acid profiles. Exploratory metabolite ratios suggested impaired substrate coordination under stress. CONCLUSIONS: Metabolic defects in PCOS are stress-dependent and not detectable at rest. Exercise training improves resting metabolism but reveals persistent impairment in adaptive lipid handling during combined insulin and lipid challenges, suggesting impaired coordination of substrate supply during metabolic stress. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ISRCTN42448814.

Humans↗

PubMed1992

11 beta-hydroxyandrostenedione in plasma, follicular fluid, and granulosa cells of women with normal and polycystic ovaries.

OBJECTIVE: To investigate the role of 11 beta-hydroxylase/11 beta-hydroxyandrostenedione (11-OHA) in the ovarian metabolism of androgens in women with polycystic ovaries (PCO) and its associated syndrome (PCOS). DESIGN: Prospective observational study examining the plasma and follicular fluid (FF) concentrations of 11-OHA, testosterone (T), androstenedione (A), and cortisol from women with PCOS and normal women in spontaneous and stimulated cycles. SETTING: The study was carried out in an infertility department and an endocrine research laboratory of a university hospital. PATIENTS: Five groups of women were studied. Blood was taken from 53 women with PCOS and 13 normal controls. Follicular fluid and blood was obtained from 51 women with stimulated cycles undergoing in vitro fertilization embryo-transfer (IVF-ET), 27 of whom had PCO and 24 had normal ovaries. Follicular fluid alone was also taken from 13 women with normal ovaries undergoing laparoscopies. INTERVENTIONS: Clear FF was obtained for analysis during oocyte collection. Granulosa cells (GCs) were obtained from seven women with PCO undergoing IVF-ET and were incubated with radiolabeled substrates. RESULTS: Circulating concentrations of T and 11-OHA were higher in women with PCOS compared with women with normal ovaries. In women with PCO receiving exogenous gonadotropin, only 11-OHA concentrations were higher. Concentrations of all steroids measured were higher in FF than plasma, with plasma 11-OHA concentrations 4 to 12 times higher in FF. Significantly lower concentrations of 11-OHA were found in the FF of women with PCO compared with women with normal ovaries. There was no evidence of 11 beta-hydroxylation of A by GCs. CONCLUSIONS: Although the raised plasma concentrations of 11-OHA may reflect hyperandrogenism in PCOS and lower 11-OHA concentrations in FF in women with PCO suggest abnormal androgen metabolism, neither can be regarded as a marker for this syndrome.

Androstenedione↗

PubMed2026

Prenatal Androgenization Modifies H3K9me3 Binding in the Promoter of the Androgen Receptor Gene in the Arcuate Nucleus of the Adult Female Mouse.

Animal models have shown that prenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS) features. We have identified that prenatally androgenized (PNA) mice modelling PCOS show suppressed androgen receptor mRNA (Ar) expression in the arcuate nucleus (ARC) across development. This could contribute to PCOS-related impaired gonadal steroid hormone feedback to GnRH neurons. However, the mechanism of Ar mRNA suppression following PNA is not determined. We performed a chromatin immunoprecipitation (ChIP) assay coupled with quantitative PCR (qPCR) to investigate histone and transcription factor binding within the Ar gene promoter or enhancer regions in the ARC of female mice at postnatal day (P)60 or gestational day (GD)18.5. In comparison to adult vehicle control (VEH) mice, our ChIP-qPCR revealed that H3K9me3, a repressive histone mark, was increased in adult PNA mice at the promoter regions of the Ar gene. H3K27ac, an active histone mark, and SP1, a transcription factor that acts as a positive regulator of gene expression, were unchanged in the same regions. Increased H3K9me3 seen at the promoter region in adult PNA mice, however, was not observed in the GD18.5 mice ARC following PNA. These results suggest that the deposition of H3K9me3 on the Ar promoter is unlikely to be established by PNA at the time of excess androgen exposure, and instead is likely to be established later in postnatal development or in adulthood. These data provide greater understanding of the developmental mechanisms and timeline underpinning PNA-mediated female dysfunction and PCOS-like reproductive physiology.

Animals↗

PubMed1978

Pituitary response to bolus and continuous intravenous infusion of luteinizing hormone-releasing factor in normal women and women with polycystic ovarian syndrome.

Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured in response to luteinizing hormone-releasing factor (LRF), given as a 100 microgram intravenous bolus and/or as a 4 hour infusion of 0.2 microgram per minute to 27 normal menstruating women and 15 women with the polycystic ovarian syndrome (PCOS). In PCOS, LH response to bolus LRF was significantly greater than those of normal women at days 1 to 4 and 8 to 10 of the cycle, whereas FSH responses were similar in all women studied. Continuous LRF infusion resulted in a biphasic LH release pattern. In normal women, the early phase was low until days 12 to 14 of the normal cycle, whereas the second phase rose progressively from the early follicular to the periovulatory period. In PCOS, the early phase was relatively large and qualitatively resembled the normal periovulatory pattern. The increased pituitary LH response to LRF in PCOS is associated with a relatively large early releasable LH pool and a low FSH response.

Adolescent↗

PubMed1992

Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance.

OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain.

Adult↗

PubMed1992

Differential effects of endothelin-1 on the vasorelaxant properties of benzopyran and non-benzopyran potassium channel openers.

1. The effects of endothelin-1 (ET-1) on the vasorelaxant properties of structurally different potassium channel openers (PCOs), BRL-38227, Ro 31-6930, SDZ PCO 400, EMD-52692, RP-49356 and pinacidil, were studied. 2. All PCOs evoked concentration-related relaxations of ET-1 (10 nM) or KCl (20 mM) contracted rat isolated aortic rings denuded of endothelium. BRL-38227, EMD 52692, SDZ PCO 400 and Ro 31-6930 were 11-42 times less potent in relaxing contractions to ET-1 than KCl. In contrast, this differential potency was not observed with RP-49356 or pinacidil. 3. BRL-38227 (0.06-3.0 microM), RP-49356 (0.3-3.0 microM) and pinacidil (0.3-3.0 microM) displaced KCl concentration-response curves to the right of controls, without modifying the maximum response. A subcontractile concentration of ET-1 (0.1 nM) prevented the inhibitory effects of low concentrations of BRL-38227 (0.06-0.1 microM) on KCl responses, but failed to modify those to RP-49356, pinacidil or high concentrations of BRL-38227 (0.3-3.0 microM). The inhibitory effects of BRL-38227 (0.1 microM) were also not changed by ET-3 (1.0 nM) or angiotensin II (0.1 nM). 4. In anaesthetized spontaneously hypertensive rats (SHR), cumulative bolus intravenous administrations of BRL-38227 (1-1000 micrograms kg-1, i.v.), Ro 31-6930 (1-1000 micrograms kg-1, i.v.), RP-49356 (10-1000 micrograms kg-1, i.v.) or nitrendipine (0.1-30 micrograms kg-1, i.v.) produced dose-dependent falls in diastolic blood pressure (DBP).ET-1 (i.v.) evoked a transient fall in DBP (1 pg kg- = 58 + 1 mmHg) which returnedto pre-administration levels within 4 min.5. Pretreatment of anaesthetized SHR with ET-l (1 pg kg-', i.v.) significantly increased the ED,5 (dose to evoke a 15% fall in DBP) values for BRL-38227 and Ro 31-6930. However, ET-l failed to modify the ED,5 values for RP-49356 or nitrendipine. The ED50 values for all of the vasodilators studied were not modified by ET-1.6. Infusion of BRL-38227 (2 pgkg-'min-', i.v.) or RP-49356 (4 pgkg-'min', i.v.) to anaesthetized SHR evoked dose-related falls in DBP, with a corresponding increase in descending aortic blood flow (DABF) and a decrease in total lower body vascular resistance (TLBVR). Pretreatment with ET-1 (1 ptg kg-', i.v.) significantly attenuated the decreases in DBP and TLBVR observed with low doses of BRL-38227, but not RP-49356 or high doses of BRL-38227. In contrast, ET-3 (3 pig kg-, i.v.) failed to modify the effects of BRL-38227 on DBP or TLBVR.7. In conscious SHR, the fall in DBP to BRL-38227 (30 pgkg-', p.o.) was significantly reduced following ET-1 (1 pig kg-', i.a.) treatment. ET-1 (1 pg kg-', i.a.) pretreatment, however, failed to modify the decrease in DBP induced by an equieffective oral dose of RP-49356 (1001pgkg-1).8. In conclusion, ET-1 selectively attenuated the vasorelaxant effects of the potassium channel opener,BRL-38227 and other substituted benzopyrans. The results are compatible with the hypothesis that benzopyran PCOs and ET-1 have affinity for a site that does not recognise RP-49356 or pinacidil. Thus,ET-l can differentiate between structurally unrelated potassium channel openers. The cardiovascular effects of some, but not all, PCOs might be radically modified in the clinical setting by elevated endogenous levels of ET-1 associated with certain diseased states.

Animals↗