Vascular Endothelial Adiponectin Signaling Across the Lifespan

Cardiovascular disease risk increases with age regardless of sex. Some of this risk is attributable to changes in natural hormones throughout the lifespan. The quintessential example of this being the dramatic increase in cardiovascular disease following the transition to menopause. Plasma levels of adiponectin, a "cardioprotective" adipokine released primarily by adipose tissue and regulated by hormones, also fluctuates throughout one's life. Plasma adiponectin levels increase with age in both men and women, with higher levels in both pre- and post- menopausal women compared to men. Younger cohorts seem to confer cardioprotective benefits from increased adiponectin levels yet elevated levels in the elderly and those with existing heart disease are associated with poor cardiovascular outcomes. Here, we review the most recent data regarding adiponectin signaling in the vasculature, highlight the differences observed between the sexes, and shed light on the apparent paradox regarding increased cardiovascular disease risk despite rising plasma adiponectin levels over time.

Seasonally Related Disruption of Metabolism by Environmental Contaminants in Male Goldfish (Carassius auratus)

Endocrine disrupting chemicals mimic or disrupt action of the natural hormones, adversely impacting hormonal function as well as cardiovascular, reproductive, and metabolic health. Goldfish are seasonal breeders with an annual reproductive cycle regulated by neuroendocrine signaling which involves allocation of metabolic energy to sustain growth and reproduction. We hypothesize that seasonal changes in physiology alter overall vulnerability of goldfish to metabolic perturbation induced by environmental contaminants. In this study, we assess effects of endogenous hormones, individual contaminants and their mixture on metabolism of goldfish at different reproductive stages. Exposure effects were assessed using 1H-NMR metabolomics profiling of male goldfish midbrain, gonad and liver harvested during early recrudescence (October), mid-recrudescence (February) and late recrudescence (June). Compounds assessed include bisphenol A, nonylphenol, bis(2-ethylhexyl) phthalate, fucosterol and a tertiary mixture (DEHP + NP + FS). Metabolome-level responses induced by contaminant exposure across tissues and seasons were benchmarked against responses induced by 17β-estradiol, testosterone and thyroid hormone (T3). We observe a clear seasonal dependence to metabolome-level alteration induced by hormone or contaminant exposures, with February (mid-recrudescence) the stage at which male goldfish are most vulnerable to metabolic perturbation. Responses induced by contaminant exposures differed from those induced by the natural hormones in a season-specific manner. Exposure to the tertiary mixture induced a functional gain at the level of biochemical pathways modeling over responses induced by individual components in select tissues and seasons. We demonstrate the importance of seasonally driven changes in physiology altering overall vulnerability of goldfish to metabolic perturbation induced by environmental contaminants, the relevance of which likely extends to other seasonally-breeding species.

Nuclear receptor modulators: Catching information by machine learning

Nuclear receptors (NRs) are involved in fundamental human health processes and are a relevant target for toxicological risk assessment. To help prioritize chemicals that can mimic natural hormones and be endocrine disruptors, computational models can be a useful tool.1,2 In this work we i) created an exhaustive collection of NR modulators and ii) applied machine learning methods to fill the data-gap and prioritize NRs modulators by building predictive models.

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis

Background: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. Methods: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. Results: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. Conclusions: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.

The Role of Biotransformation in the Activity of Endocrine Disruptors

: An “endocrine disruptor” has been broadly defined as an exogenous chemical that interferes with the production, release, transport, metabolism, binding, action, or elimination of endogenous hormones which are responsible for homeostasis, reproduction, development or behaviour. Diverse groups of chemicals such as pharmaceuticals, phytoestrogens, natural hormones, and synthetic chemicals such as pesticides, plasticizers, phthalates, parabens, polychlorinated/polybrominated biphenyls, bisphenols are shown to interfere with the endocrine system and defined as EDs in the last three decades. As for all chemicals, the biotransformation of EDs has a decisive role in their potential toxic effects. Humans are exposed to vast amounts of diverse chemicals throughout their life. Fortunately, most of the chemicals are converted, via biotransformation reactions catalysed by enzymes, into more hydrophilic metabolites, which are readily excreted in urine or bile. Biotransformation reactions resulting in less toxic metabolites are known as detoxification. However, some biotransformation reactions are called bioactivation in which more toxic metabolites are formed. In the case of EDs, metabolites formed via bioactivation usually have a higher affinity for a hormone receptor or induce/inhibit an enzyme involved in the synthesis or catabolism of an endogenous hormone more dramatically compared to their parent compound. In the present review, the role of bioactivation in endocrine modulating effects of chemicals from all groups of Eds is highlighted, namely endogenous estrogens, phytoestrogens, synthetic/industrial chemicals, and pharmaceuticals.

Student Project A comparison of natural & synthetic rooting hormones for cuttings propagation using Saxagothea conspicua Lindl.

This paper examines the effects of using natural and synthetic rooting hormones for cuttings propagation. The study used Saxegothaea conspicua Lindl, a Near Threatened conifer native to Chile and Argentina. A trial was set on 80 semi-ripe cuttings of S. conspicua applying both synthetic (IBA) and natural hormones derived from willow and lentils. This study evaluates and measures the rooting success of using different types of hormones at the end of the trial (such as development of roots, length, etc). It also aims to examine the level and type of auxins found in the lentil and willow rooting solution, if present. After evaluation of results of the present trial and the wider literature, this paper discusses the potential use of this type of natural hormones in future. This article is an extract from the author’s HND Specialist Project written for the RBGE Diploma in Horticulture with Plantsmanship in June 2018.

Serum nesfatin in overweight and obese children

BACKGROUND: Obesity is one of the most common children diseases. In present time it is being actively studied the natural hormones role in the pathogenesis of obesity. AIMS: To determine the relationship between serum nesfatin level with impaired lipid metabolism in school age children with overweight and obesity. MATERIALS AND METHODS: The study included children with overweight and obesity (case) and healthy children with normal body mass (control) aged 9 to 15 years. All children were determined by concentration in cholesterol blood and its factions, apoA-1, apoB. Enzyme-linked immunosorbent assay (Bio Human Nesfatin Enzyme Immunoassay Kit). RESULTS: Groups of patients with overweight and obesity (n = 53) and healthy children (n = 31) were comparable by age and sex. In obese children, a significant decrease in the level of nesfatin-1 was revealed compared with the group with normal body weight. In cases of children obesity there is a marked decrease in the concentration of nesfatin-1 in serum, especially expressed in the dyslipidemia presence. The nesfatin-1 level are negatively correlated to BMI and body fat content. CONCLUSIONS: The obtained data suggest that along with the known key role of nesfatin in the regulation of eating behavior and appetite, it also affects anthropometric indicators, primarily associated with the accumulation of excess fat mass. Based on the data obtained, nesfatin-1 should be considered as a possible marker for the development of obesity in children.

Changes in daily life reduce indoor exposure to selected endocrine disruptors in the home environment: a pilot intervention study

Increasing prevalence of lifestyle diseases raised global awareness about health consequences of human exposure to endocrine disruptors (EDs): synthetic chemicals that mimic natural hormones and affect the biochemical and endocrine balance. As home environment is one of the main sources of the exposure to xenobiotics – especially for pregnant women, infants and young children – health organizations emphasize the need of implementing lifestyle changes to protect human health and child development. The aim of this study was to evaluate the effectiveness of introducing changes in daily life in lowering the exposure to selected EDs in the indoor home environment. Twenty-six healthy volunteers from 9 households from Gdansk (Poland) were enrolled and their home- and lifestyle-related exposure to EDs was analyzed using a designed questionnaire and algorithm. Urine and dust samples were collected before and after introducing the recommended lifestyle changes. The concentrations of selected EDs in the samples were determined using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). This pilot study confirmed the ubiquity of harmful chemicals in the home environment and the importance of exposure related to a daily routine. Importantly, it proved that lifestyle modifications implemented by participants led to a significant decrease in both, their home-related exposure to EDs, as well as in urine concentrations of these chemicals. It also demonstrated a need for determining EDs exposure and introducing lifestyle changes as a useful tool for prevention of lifestyle-related diseases.

Pharmacological Modulation of Steroid Activity in Hormone-Dependent Breast and Prostate Cancers: Effect of Some Plant Extract Derivatives

The great majority of breast and prostate tumors are hormone-dependent cancers; hence, estrogens and androgens can, respectively, drive their developments, making it possible to use pharmacological therapies in their hormone-dependent phases by targeting the levels of steroid or modulating their physiological activity through their respective nuclear receptors when the tumors relapse. Unfortunately, at some stage, both breast and prostate cancers become resistant to pharmacological treatments that aim to block their receptors, estrogen (ER) or androgen (AR) receptors, respectively. So far, antiestrogens and antiandrogens used in clinics have been designed based on their structural analogies with natural hormones, 17-β estradiol and dihydrotestosterone. Plants are a potential source of drug discovery and the development of new pharmacological compounds. The aim of this review article is to highlight the recent advances in the pharmacological modulation of androgen or estrogen levels, and their activity through their cognate nuclear receptors in prostate or breast cancer and the effects of some plants extracts.