Search Results
Department of Medicine-Western Health, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia
Search for other papers by Alexander Tacey in
Google Scholar
PubMed
Institute for Physical Activity and Nutrition, Deakin University, Geelong, Victoria, Australia
Search for other papers by Lewan Parker in
Google Scholar
PubMed
Search for other papers by Bu B Yeap in
Google Scholar
PubMed
Search for other papers by John Joseph in
Google Scholar
PubMed
Search for other papers by Ee M Lim in
Google Scholar
PubMed
Search for other papers by Andrew Garnham in
Google Scholar
PubMed
Search for other papers by David L Hare in
Google Scholar
PubMed
Search for other papers by Tara Brennan-Speranza in
Google Scholar
PubMed
Department of Medicine-Western Health, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia
Search for other papers by Itamar Levinger in
Google Scholar
PubMed
The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% (P < 0.05). Baseline blood glucose was elevated following prednisolone compared to placebo (P < 0.001). Three hours post exercise, blood glucose in the prednisolone trial was reduced to a level equivalent to the baseline concentration in the placebo trial (P > 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise (P < 0.05). Total white blood cell count was elevated at all time-points with prednisolone (P < 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone (P < 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels.
Search for other papers by Katarzyna Wyskida in
Google Scholar
PubMed
Search for other papers by Grzegorz Franik in
Google Scholar
PubMed
Search for other papers by Tomasz Wikarek in
Google Scholar
PubMed
Search for other papers by Aleksander Owczarek in
Google Scholar
PubMed
Search for other papers by Alham Delroba in
Google Scholar
PubMed
Search for other papers by Jerzy Chudek in
Google Scholar
PubMed
Search for other papers by Jerzy Sikora in
Google Scholar
PubMed
Search for other papers by Magdalena Olszanecka-Glinianowicz in
Google Scholar
PubMed
Context
The aim of this study was to assess the plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 levels in relation to hormonal changes during the menstrual cycle in young, healthy, normal-weight women.
Methods
The study involved 52 young, healthy, normal-weight women. Anthropometric parameters, body composition and levels of plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 in addition to serum FSH, LH, estradiol, progesterone, 17-OH progesterone, androgens, SHBG and insulin concentrations were measured during a morning in fasting state three times: between days 2–4, days 12–14 and days 24–26 of the menstrual cycle.
Results
Plasma adiponectin, omentin-1, resistin and visfatin/NAMPT, apelin, TNF-α, IL-6 and RBP4 concentrations were stable during the menstrual cycle, while leptin and vaspin levels were significantly higher in both the midcycle and the luteal phases than those in the follicular phase. Multivariate regression analyses revealed that changes in leptin and vaspin levels between the follicular and the luteal phase are strongly related to changes in total testosterone levels.
Conclusions
Our results revealed stable levels of adipokines during the phases of the physiological menstrual cycle, except for leptin and vaspin, which showed increased levels in both the midcycle and the luteal phases. This effect was significantly associated with changes in the secretion of testosterone, 17-OH progesterone and insulin in the luteal phase.
Search for other papers by Jennifer K Y Ko in
Google Scholar
PubMed
Search for other papers by Thomas F J King in
Google Scholar
PubMed
Search for other papers by Louise Williams in
Google Scholar
PubMed
Search for other papers by Sarah M Creighton in
Google Scholar
PubMed
Search for other papers by Gerard S Conway in
Google Scholar
PubMed
Objective
To review the treatment choices of women with complete androgen insensitivity syndrome (CAIS) at a single tertiary centre.
Design
Retrospective review.
Patients
Women with CAIS identified from our database.
Results
The study group comprised 141 women with CAIS. Eleven percent (16/141) of women had gonads in situ, 3 of whom were under workup for gonadectomy. The age of gonadectomy in the remainder 125 women was 17 (0.1–53) years. The most common form of HRT was oral oestrogen or transdermal oestrogen in 80% (113/141). 13/141 (9%) women used vaginal oestrogens alone or together with other forms of HRT. Testosterone preparations had been used by 17% (24/141) of women and were currently used in 10% (14/141). Of those who had used testosterone, 42% (10/24) had chosen not to continue after a therapeutic trial.
Conclusions
In a clinic offering individualised multidisciplinary care for women with CAIS, we found that the majority of women chose oestrogen-based treatment while a significant minority used testosterone.
Search for other papers by T S Nilsen in
Google Scholar
PubMed
Search for other papers by L Thorsen in
Google Scholar
PubMed
Search for other papers by C Kirkegaard in
Google Scholar
PubMed
Search for other papers by I Ugelstad in
Google Scholar
PubMed
Search for other papers by S D Fosså in
Google Scholar
PubMed
Search for other papers by T Raastad in
Google Scholar
PubMed
Background
Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT.
Methods
Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG) (n=16) or a control group (CG) (n=15) for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV), HSP60) and indicators of muscle cellular stress (heat shock protein (HSP) 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins) using Western blot and ELISA.
Results
No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups.
Conclusion
Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.
Search for other papers by Angela Köninger in
Google Scholar
PubMed
Search for other papers by Philippos Edimiris in
Google Scholar
PubMed
Search for other papers by Laura Koch in
Google Scholar
PubMed
Search for other papers by Antje Enekwe in
Google Scholar
PubMed
Search for other papers by Claudia Lamina in
Google Scholar
PubMed
Search for other papers by Sabine Kasimir-Bauer in
Google Scholar
PubMed
Search for other papers by Rainer Kimmig in
Google Scholar
PubMed
Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany
Search for other papers by Hans Dieplinger in
Google Scholar
PubMed
Oxidative stress seems to be present in patients with polycystic ovary syndrome (PCOS). The aim of this study was to evaluate the correlation between characteristics of PCOS and serum concentrations of afamin, a novel binding protein for the antioxidant vitamin E. A total of 85 patients with PCOS and 76 control subjects were investigated in a pilot cross-sectional study design between 2009 and 2013 in the University Hospital of Essen, Germany. Patients with PCOS were diagnosed according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Afamin and diagnostic parameters of PCOS were determined at early follicular phase. Afamin concentrations were significantly higher in patients with PCOS than in controls (odds ratio (OR) for a 10 mg/ml increase in afamin=1.3, 95% CI=1.08–1.58). This difference vanished in a model adjusting for age, BMI, free testosterone index (FTI), and sex hormone-binding globulin (SHBG) (OR=1.05, 95% CI=0.80–1.38). In patients with PCOS, afamin correlated significantly with homeostatic model assessment-insulin resistance (HOMA-IR), fasting glucose, BMI, FTI, and SHBG (P<0.001), but in a multivariate linear model, only HOMA-IR remained significantly associated with afamin (P=0.001). No correlation was observed between afamin and androgens, LH, FSH, LH/FSH ratio, antral follicle count, ovarian volume, or anti-Müllerian hormone. In conclusion, elevated afamin values may indicate a state of oxidative stress and inflammation, strongly associated with IR and offering an indicator of impaired glucose tolerance in patients with PCOS irrespective of obesity.
Search for other papers by Neil R Chappell in
Google Scholar
PubMed
Search for other papers by Beth Zhou in
Google Scholar
PubMed
Search for other papers by Amy K Schutt in
Google Scholar
PubMed
Search for other papers by William E Gibbons in
Google Scholar
PubMed
Search for other papers by Chellakkan S Blesson in
Google Scholar
PubMed
Polycystic ovary syndrome (PCOS) is the most common ovulatory defect in women. Although most PCOS patients are obese, a subset of PCOS women are lean but show similar risks for adverse fertility outcomes. A lean PCOS mouse model was created using prenatal androgen administration. This developmentally programmed mouse model was used for this study. Our objective was to investigate if mitochondrial structure and functions were compromised in oocytes obtained from lean PCOS mouse. The lean PCOS mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were isolated and were used to investigate inner mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance and electron microscopy. Our results demonstrate that lean PCOS mice have similar weight to that of the controls but exhibit glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of their oocytes show impaired inner mitochondrial membrane function, elevated reactive oxygen species (ROS) and increased RNA transcript abundance. Electron microscopy of the oocytes showed impaired mitochondrial ultrastructure. In conclusion, the lean PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial ultrastructure and function.
Search for other papers by Zofia Kolesinska in
Google Scholar
PubMed
Search for other papers by James Acierno Jr in
Google Scholar
PubMed
Search for other papers by S Faisal Ahmed in
Google Scholar
PubMed
Search for other papers by Cheng Xu in
Google Scholar
PubMed
Search for other papers by Karina Kapczuk in
Google Scholar
PubMed
Search for other papers by Anna Skorczyk-Werner in
Google Scholar
PubMed
Search for other papers by Hanna Mikos in
Google Scholar
PubMed
Search for other papers by Aleksandra Rojek in
Google Scholar
PubMed
Search for other papers by Andreas Massouras in
Google Scholar
PubMed
Search for other papers by Maciej R Krawczynski in
Google Scholar
PubMed
Search for other papers by Nelly Pitteloud in
Google Scholar
PubMed
Search for other papers by Marek Niedziela in
Google Scholar
PubMed
46,XY differences and/or disorders of sex development (DSD) are clinically and genetically heterogeneous conditions. Although complete androgen insensitivity syndrome has a strong genotype–phenotype correlation, the other types of 46,XY DSD are less well defined, and thus, the precise diagnosis is challenging. This study focused on comparing the relationship between clinical assessment and genetic findings in a cohort of well-phenotyped patients with 46,XY DSD. The study was an analysis of clinical investigations followed by genetic testing performed on 35 patients presenting to a single center. The clinical assessment included external masculinization score (EMS), endocrine profiling and radiological evaluation. Array-comparative genomic hybridization (array-CGH) and sequencing of DSD-related genes were performed. Using an integrated approach, reaching the definitive diagnosis was possible in 12 children. The correlation between clinical and genetic findings was higher in patients with a more severe phenotype (median EMS 2.5 vs 6; P = 0.04). However, in 13 children, at least one variant of uncertain significance was identified, and most times this variant did not correspond to the original clinical diagnosis. In three patients, the genetic studies guided further clinical assessment which resulted in a reclassification of initial clinical diagnosis. Furthermore, we identified eight patients harboring variants in more than one DSD genes, which was not seen in controls (2.5%; P = 0.0003). In summary, taking into account potential challenges in reaching the definitive diagnosis in 46,XY DSD, only integrated approach seems to be the best routine practice.
Search for other papers by María J Gómora in
Google Scholar
PubMed
Search for other papers by Flavia Morales-Vásquez in
Google Scholar
PubMed
Search for other papers by Enrique Pedernera in
Google Scholar
PubMed
Search for other papers by Delia Perez-Montiel in
Google Scholar
PubMed
Search for other papers by Horacio López-Basave in
Google Scholar
PubMed
Search for other papers by Antonio R Villa in
Google Scholar
PubMed
Search for other papers by Azucena Hernández-Martínez in
Google Scholar
PubMed
Search for other papers by Esteban Mena in
Google Scholar
PubMed
Search for other papers by Carmen Mendez in
Google Scholar
PubMed
The significance of the presence of androgen receptor (AR), estrogen receptor alpha (ER) and progesterone receptor (PR) in ovarian cancer patient survival has been a matter of numerous studies. This study was aimed to describe the expression profile of the three sexual steroid receptors in high-grade serous, endometrioid, mucinous and low-grade serous ovarian carcinoma and its association to the proliferation index in patients with primary ovarian carcinoma diagnosis, before any treatment. Eighty-one samples were obtained from the National Institute of Cancerology in Mexico City and were evaluated for the presence of AR, ER, PR and Ki67 by immunohistochemistry. The four subtypes of ovarian carcinoma displays a specific profile of the eight possible combinations of the steroid receptors with significant differences within the profile and the histological subtypes. High-grade serous carcinoma was characterized by a high frequency of both, triple-negative and AR+ ER− PR+ profiles. Endometrioid carcinoma presented a higher frequency of triple-positive profile. The presence of only AR+ profile was not observed in the endometrioid tumors. The relationship of the receptor profile with the proliferation index in the tumor epithelium shows that the expression of only ER is associated to a reduced proliferation index in endometrioid carcinoma. Steroid hormone receptor expression and co-expression could help characterize ovarian carcinoma.
Search for other papers by M Axelstad in
Google Scholar
PubMed
Search for other papers by U Hass in
Google Scholar
PubMed
Search for other papers by M Scholze in
Google Scholar
PubMed
Search for other papers by S Christiansen in
Google Scholar
PubMed
Search for other papers by A Kortenkamp in
Google Scholar
PubMed
Search for other papers by J Boberg in
Google Scholar
PubMed
Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.
Search for other papers by Hong Tang in
Google Scholar
PubMed
Search for other papers by Xiaomei Jiang in
Google Scholar
PubMed
Search for other papers by Yu Hua in
Google Scholar
PubMed
Search for other papers by Heyue Li in
Google Scholar
PubMed
Search for other papers by Chunlan Zhu in
Google Scholar
PubMed
Search for other papers by Xiaobai Hao in
Google Scholar
PubMed
Search for other papers by Minhui Yi in
Google Scholar
PubMed
Search for other papers by Linxia Li in
Google Scholar
PubMed
Background
Polycystic ovary syndrome (PCOS) is an androgen disorder and ovarian dysfunction disease in women of reproductive age. The cell death of granulosa cells (GCs) plays an important role in the development of PCOS. However, the mechanism of GC death is still unclear.
Methods
In the current study, NEDD4L was found to be elevated in PCOS GEO (Gene Expression Omnibus) databases and mouse models. The cell viability was analyzed by CCK-8 and FDA staining. The expression of ferroptosis markers was assessed by ELISA and immunofluorescence. The direct interaction of GPX4 and NEDD4L was verified by co-immunoprecipitation assay.
Result
Functionally, results from CCK-8 and FDA staining demonstrated that NEDD4L inhibited the cell viability of KGN cells and NEDD4L increased the levels of iron, malonyldialdehyde, and reactive oxygen species and decreased glutathione levels. Moreover, the cell death of KGN induced by NEDD4L was blocked by ferroptosis inhibitor, suggesting that NEDD4L regulates KGN cell ferroptosis. Mechanistically, NEDD4L directly interacts with GPX4 and promotes GPX4 ubiquitination and degradation.
Conclusion
Taken together, our study indicated that NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of PCOS.