Corticosteroid Levels Research Articles

Variation in nest building, aggression, learning, and steroid hormone levels in Betta splendens

Individuals within a population present behavioral responses that vary according to intrinsic and extrinsic factors such as ontogenetic phase, nutritional status, reproductive stage, and previous experiences. These differences can be explained by endogenous changes, such as hormone release, that can modulate reproductive behaviors, stress response, and cognitive processes. In order to investigate the relationship between behavior and hormonal levels in the fighting fish Betta splendens, the present study characterized nest building, aggressive behavior, learning of a task, and levels of cortisol and 11-ketotestosterone (11-KT) in 86 male Fighting fish. At the beginning of the experiment (days 1–4), fish were characterized as nest builders, intermediate builders, or non-builders. They were then sequentially tested for aggression (days 7–8), learning performance (days 11–21), and circulating hormone levels (day 23). Nest builders showed the lowest hormonal levels at the end of the experiment and low aggressiveness; Intermediate builders presented low cortisol, but high KT levels and best learned the task; Non-builders were the most aggressive animals with higher cortisol levels (at day 23). Our data suggest that in B. splendens, aggressive behavior and learning performance are related to the relative investment in reproduction and variation in circulating levels of corticosteroids and androgens.

Comparing metabolic profiles between female endurance athletes and non-athletes reveals differences in androgen and corticosteroid levels

Endurance training is associated with physiological changes in elite athletes, but little is known about female-specific effects of endurance training. Despite the significant rise in female sports participation, findings from studies performed on male athletes are largely extrapolated to females without taking into consideration sex-specific differences in metabolism. Subsequently, this study aimed to investigate the steroid hormone profiles of elite female endurance athletes in comparison with their non-athletic counterparts. Untargeted metabolomics-based mass spectroscopy combined with ultra-high-performance liquid chromatography was performed on serum samples from 51 elite female endurance athletes and 197 non-athletic females. The results showed that, compared to non-athletic females, certain androgen, pregnenolone, and progestin steroid hormones were reduced in elite female endurance athletes, while corticosteroids were elevated. The most significantly altered steroid hormones were 5alpha-androstan-3alpha,17alpha-diol monosulfate (FDR = 1.90 × 10-05), androstenediol (3alpha, 17alpha) monosulfate (FDR = 2.93 × 10-04), and cortisol (FDR = 2.93 × 10-04). Conclusively, the present study suggests that elite female endurance athletes have a unique steroid hormone profile with implications on their general health and performance.

Selection for winners impacts the endocrine system in the Siamese fighting fish

In southeast Asia, males of the Siamese fighting fish, Betta splendens, have been selected across centuries for winning paired staged fights and previous work has shown that males from fighter strains are more aggressive than wild-types. This strong directional selection for winners is likely to have targeted aggression-related endocrine systems, and a comparison between fighter and wild-type strains can bring into evidence the key hormones implicated in aggression. Here, we compared the plasma levels of the androgen 11-ketotestosterone (KT) and of the corticosteroid cortisol (F) in F2 males of a fighter and a wild-type strain raised under similar laboratory conditions. We show that F was generally lower in fighter as compared with wild-type males, while no overall differences in KT levels were detected between strains. When presented with a mirror-induced aggressive challenge, post-fight levels of F increased but more significantly so in wild-type males, while KT increased in males of both strains. After the challenge, fighter males had higher levels of KT as compared with wild-type males, while the pattern for F was opposite. As compared with animals in social groups, wild-type males placed under social isolation had lower F levels, while KT decreased for fighters.Taken together, this data suggests that while wild-type males responded to aggression with an increase in circulating levels of both androgens and corticosteroids, males selected for winning fights maintained a blunt F response, increasing only KT levels. These data agree with the hypothesis that a combination of high levels of androgens and low levels of corticosteroids is associated with high aggression. Overall, these results seem to indicate that selection for winning had a stronger impact in the hypothalamus-pituitary-interrenal axis than in the hypothalamus-pituitary–gonadal axis in B. splendens.

The Anti-Obesity Potential of Cyperus rotundus Extract Containing Piceatannol, Scirpusin A and Scirpusin B from Rhizomes: Preclinical and Clinical Evaluations.

PurposeObesity is a complex medical problem that increases the risk of other diseases like diabetes, cardiovascular diseases, and fatty liver disease. The present study evaluated the efficacy and safety of Cyperus rotundus rhizome extract (CRE), standardized to contain Piceatannol, Scirpusin A, and Scirpusin B (5% total Stilbenoids) in overweight individuals. The mechanism of activity was evaluated in a diet-induced mice model of obesity and adipocytes in vitro.Materials and MethodsThe efficacy, safety, and tolerability of CRE were evaluated in 30 obese individuals with a BMI of 30 to 40 kg/m2 for 90 days in a randomized, double-blind, parallel-group, placebo-controlled study. In vitro studies were carried out in differentiated 3T3 L1 adipocytes, and the therapeutic efficacy was evaluated in high-fat diet-induced obese mice.ResultsThe pilot clinical study showed a reduction in body weight with a significant decrease in waist circumference and BMI. The serum lipid profile showed a significant improvement in CRE-treated individuals. The extract was well tolerated, and no adverse effects were reported at the end of the study. CRE showed a dose-dependent adipogenesis reduction in vitro with an IC50 value of 9.39 μg/mL, while oral administration of CRE reduced weight gain in diet-induced obese mice. The efficacy in mice was associated with reduced levels of leptin, corticosteroids, and serum lipid levels, with no adverse effects.ConclusionCRE has anti-adipogenic properties, is safe for human consumption, and effectively manages weight and hypercholesterolemia in overweight individuals.

Topical Corticosteroids in the Treatment of Vulvar Lichen Sclerosus: A Review of Pharmacokinetics and Recommended Dosing Frequencies.

Topical corticosteroids are often utilized as the first-line treatment for vulvar lichen sclerosus (VLS). However, there is wide variability in dosing regimens, as well as a lack of consensus on maintenance dosing. Available guidelines on dosing frequency and regimen continuation for VLS are based on clinical expert opinion and do not necessarily reflect the pharmacokinetics of topical corticosteroids. Over the past few decades, there have been many advances in the techniques used to measure the local and systemic absorption of topical corticosteroids. These techniques have led to a greater understanding of the pharmacokinetics and bioavailabilities of these medications. However, it is not clear how this new information has been applied in evaluating dosing regimens and commonly cited risks when considering short- and long-term use in different vulvar dermatoses. This purpose of this review is to evaluate the available evidence on pharmacokinetics, absorption rates, and concentration levels of topical corticosteroids in lesional and nonlesional skin. Additionally, the evidence regarding commonly cited risks of topical corticosteroid use, including dermal thinning, adrenal suppression, systemic immunosuppression, and tachyphylaxis are reviewed. Differences in the effects of topical corticosteroids on the varied tissues of the vulva are specifically explored. Finally, these considerations are applied to evaluate the current treatment guidelines for VLS to provide direction in determining an evidenced-based dosing regimen and to inform future research in this area. Mautz TT, Krapf JM, Goldstein AT. Topical Corticosteroids in the Treatment of Vulvar Lichen Sclerosus: A Review of Pharmacokinetics and Recommended Dosing Frequencies. Sex Med Rev 2022;10:42-52.

Comparative study on molecular mechanism of diabetic myopathy in two different types of streptozotocin-induced diabetic models

AimsStreptozotocin (STZ)-induced diabetic animal models have been widely used to study diabetic myopathy; however, non-specific cytotoxic effects of high-dose STZ have been discussed. The purpose of this study was to compare diabetic myopathy in a high-STZ model with another well-established STZ model with reduced cytotoxicity (high-fat diet (HFD) and low-dose STZ) and to identify mechanistic insights underlying diabetic myopathy in STZ models that can mimic perturbations observed in human patients with diabetic myopathy. Main methodsMale C57BL6 mice were injected with a single high dose of STZ (180 mg/kg, High-STZ) or were given HFD plus low-dose STZ injection (STZ, 55 mg/kg/day, five consecutive days, HFD/STZ). We characterized diabetic myopathy by histological and immunochemical analyses and conducted gene expression analysis. Key findingsThe high-STZ model showed a significant reduction in tibialis anterior myofiber size along with decreased satellite cell content and downregulation of inflammation response and collagen gene expression. Interestingly, blood corticosteroid levels were significantly increased in the high-STZ model, which was possibly related to lowered inflammation response-related gene expression. Further analyses using the HFD/STZ model showed downregulation of gene expression related to mitochondrial functions accompanied by a significant decrease in ATP levels in the muscles. SignificanceThe high-STZ model is suitable for studies regarding not only severe diabetic myopathy with excessive blood glucose but also negative impact of glucocorticoids on skeletal muscles. In contrast, the HFD/STZ model is characterized by higher immune responses and lower ATP production, which also reflects the pathologies observed in human diabetic patients.

Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder.

Ghrelin may influence several alcohol-related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD). We used serum samples from a randomized, crossover, double-blind, placebo-controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3µg/kg) followed by continuous infusion (16.9ng/kg/min) of acyl ghrelin or placebo. The first experiment included an IV alcohol self-administration (IV-ASA) session and the second experiment included an IV alcohol clamp (IV-AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session. In both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV-ASA q-value=0.0003 and IV-AC q<0.0001), corticosterone (IV-ASA q=0.0202 and IV-AC q<0.0001), and glycochenodeoxycholic acid (IV-ASA q=0.0375 and IV-AC q=0.0013). In the IV-ASA experiment, ghrelin infusion increased levels of cortisone (q=0.0352) and fatty acids 18:1 (q=0.0406) and 18:3 (q=0.0320). Moreover, in the IV-AC experiment, ghrelin infusion significantly increased levels of glycocholic acid (q<0.0001) and phenylalanine (q=0.0458). IV ghrelin infusion, combined with IV alcohol administration, was associated with increases in the circulating metabolite levels of corticosteroids and glycine-conjugated bile acids, among other changes. Further research is needed to understand the role that metabolomic changes play in the complex interaction between ghrelin and alcohol.

Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium.

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.

Plasma Metabolomics in a Nonhuman Primate Model of Abdominal Radiation Exposure.

The acute radiation syndrome is defined in large part by radiation injury in the hematopoietic and gastrointestinal (GI) systems. To identify new pathways involved in radiation-induced GI injury, this study assessed dose- and time-dependent changes in plasma metabolites in a nonhuman primate model of whole abdominal irradiation. Male and female adult Rhesus monkeys were exposed to 6 MV photons to the abdomen at doses ranging between 8 and 14 Gy. At time points from 1 to 60 days after irradiation, plasma samples were collected and subjected to untargeted metabolomics. With the limited sample size of females, different discovery times after irradiation between males and females were observed in metabolomics pattern. Detailed analyses are restricted to only males for the discovery power. Radiation caused an increase in fatty acid oxidation and circulating levels of corticosteroids which may be an indication of physiological stress, and amino acids, indicative of a cellular repair response. The largest changes were observed at days 9 and 10 post-irradiation, with most returning to baseline at day 30. In addition, dysregulated metabolites involved in amino acid pathways, which might indicate changes in the microbiome, were detected. In conclusion, abdominal irradiation in a nonhuman primate model caused a plasma metabolome profile indicative of GI injury. These results point to pathways that may be targeted for intervention or used as early indicators of GI radiation injury. Moreover, our results suggest that effects are sex-specific and that interventions may need to be tailored accordingly.

Adrenal Corticosteroid Perturbation by the Endocrine Disruptor BDE-47 in a Human Adrenocortical Cell Line and Male Rats.

Polybrominated diphenyl ethers (PBDEs) have been previously shown to alter various endocrine biosynthetic pathways. Growing epidemiological evidence suggests that PBDEs alter cardiovascular function. The goal of this study was to examine the effects of BDE-47 on adrenal corticosteroid pathways that play vital roles in cardiovascular homeostasis and pathophysiology. The effect of BDE-47 on aldosterone and cortisol secretion was characterized in a human adrenocortical cell line. HAC15 cells were exposed to various concentrations of BDE-47 (1 nM to 100 μM). Cell viability, corticosteroid secretion, gene expression of enzymes involved in corticosteroid synthesis, and metabolic activity was examined. Additionally, Sprague Dawley male rats were orally exposed to BDE-47 (10 or 100 µg/kg), 5 days per week for 16 weeks. Organ weights and plasma corticosteroid levels were measured. In HAC15 cells, basal and stimulated aldosterone and cortisol secretion was significantly increased by BDE-47. Gene expression of several enzymes involved in corticosteroid synthesis and mitochondrial metabolism also increased. In Sprague Dawley rats, adrenal but not heart, kidney, or liver weights, were significantly increased in BDE-47 treatment groups. Plasma corticosterone levels were significantly increased in the 100 µg BDE-47/kg treatment group. No change in plasma aldosterone levels were observed with BDE-47 exposure. These data indicate that BDE-47 disrupts the regulation of corticosteroid secretion and provides further evidence that PBDEs are potential endocrine disruptors. Future studies will determine the underlying molecular mechanism of altered corticosteroid production and examine whether these alterations result in underlying cardiovascular disease in our rodent model of 16-week BDE-47 exposure.

Physiological markers suggest energetic and nutritional adjustments in male sharks linked to reproduction.

Energetic condition is one of the most important factors that influence fitness and reproductive performance in vertebrates. Yet, we lack evidence on how energetic states change in response to reproduction in large marine vertebrates. In the present study, we used a non-lethal approach to assess relationships among reproductive stage, circulating steroid hormones (testosterone and relative corticosteroid levels), plasma fatty acids, and the ketone body β-hydroxybutyrate in male sharks of two species with divergent ecologies, the benthic nurse shark (Ginglymostoma cirratum) and the epipelagic blacktip shark (Carcharhinus limbatus). We found higher relative corticosteroid levels in adult nurse sharks during the pre-mating period and in blacktip sharks during the mating period. Higher levels of β-hydroxybutyrate were found in adult nurse sharks during the mating period, but concentrations of this ketone body did not significantly vary across reproductive stages in blacktip sharks. We also detected reduced percentages of essential fatty acids during the mating period of both nurse and blacktip sharks. Taken together, our findings suggest that nurse and blacktip sharks differ in their energetic strategy to support reproduction, however, they likely rely on physiologically important fatty acids during mating, to support spermatogenesis.

Are high dose steroids are preferable than low dose steroids in COVID 19 pneumonia?

Background: In COVID 19 there is systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction. It has been proposed that the potent anti-inflammatory effects of corticosteroids might prevent or mitigate these deleterious effects. Conversly at the other end of the dose range high levels of corticosteroids are immunosuppressive and can increase risk of fatal infection including sepsis. Giving optimal level of corticosteroids at the right time is vital to control infections and restore homeostasis. Aim: The aim of the study is to compare benefits and side effects of high dose corticosteroids and low dose corticosteroids in treatment of covid 19 pneumonia. Materials and Methods: This study is retrospective, observational study of 80 patients diagnosed with covid 19 pneumonia. They were divided into two groups, one group of patients received low dose of steroids (0.5-1mg/kg/day for 7-10days) and other group of patients received high dose of steroids(>250mg/day for 7-10days).In these two groups of patients we compared duration of hospital stay, duration of oxygen support, mortality rate of the patients. These group of patients are followed up for development of side effects of corticosteroids, here we look into three side effects-recurrent infections, poorly controlled diabetes and skin manifestations. Data was analysed. Results: Out of 80 patients (40 in high dose group and 40 in low dose group) mean duration of hospital stay and mean number of days of oxygen support were more in high dose group compared to low dose group. However, the difference was not found to be statistically significant (P value >0.05). In low dose group 22.5% died as compared to 40% in high dose group. However, on performing chi square test, this difference was not found to be statistically significant (P value >0.05). In low dose group 3.2% had complications as compared to 25% in high dose group. On performing chi square test, this difference was found to be statistically significant (P value

Central Serous Retinopathy in a Post COVID-19 Asymptomatic Healthcare Worker at a Tertiary Care Hospital: A Unique Case Report

Aim: Early detection and management of stress-related Central Serous Retinopathy caused due to COVID-19.&#x0D; Background: CSR has been associated with stress and is usually self-resolving. COVID-19 is known to induce psychological stress and its effects are many, one of them may be CSR. The importance of understanding the psychological impact of the disease, its consequences, and the counseling of even asymptomatic patients to ensure stress reduction needs to be understood by the treating physician.&#x0D; Case Report and Discussion: We report the first case of CSR associated with COVID-19 related stress in an asymptomatic health care worker and the follow-up and treatment plan for this case. It has been shown that unfavourable psychic factors influence endogenous hormonal secretion which in turn increases the levels of corticosteroids and catecholamines which have been found to induce CSR.&#x0D; Conclusion: This study highlights the importance of understanding the psychological effect of the pandemic and recognising this and early treatment will reduce the ill effects of the stress induced by COVID-19.

Systematic review of single and combined treatments for different types of striae: a comparison of striae treatments.

Striae distensae (SD) or stretch marks are among the most common forms of atrophic scarring and cosmetic problems, especially in women, that negatively affect quality of life. The main causes of SD vary widely, but the most significant ones include obesity, pregnancy, high corticosteroid levels, weight changes, endocrine disorders and genetic predispositions. Various modalities are available for the treatment of SD; however, there is still no gold standard therapy for this condition. Given the many questions concerning the preferred therapeutic modalities for SD or their overall cost-effectiveness, this comprehensive systematic review discusses the most prevalent, recent and promising therapies for SD in three main categories, including single therapy, therapeutic comparisons and combination therapy. A systematic search was carried out in Medline, Scopus, Web of Science and Google Scholar for original articles published on the treatment of SD by 20 May 2019. One hundred articles were reviewed and divided into three categories. In the single therapy category, we found that laser and other light-based devices and topical treatments are the most commonly applied interventions. In the therapeutic comparison category, we found that most of the common therapeutic modalities are equally effective and there is no significant difference between them in side-effects and treatment duration. In the combination therapy category, we found that the combination of two or more modalities is usually better than using each one alone.

Androgens and corticosteroids increase in response to mirror images and interacting conspecifics in males of the Siamese fighting fish Betta splendens

The role of hormones as modulators of aggressive behavior in fish remains poorly understood. Androgens and corticosteroids, in particular, have been associated with aggressive behavior in fish but it is still not clear if animals adjust the secretion of these hormones to regulate behavior during ongoing fights, in response to fight outcomes in order to adjust aggressive behavior in subsequent fights, or both. With its stereotyped displays and high aggression levels, the Siamese fighting fish Betta splendens is an excellent model to investigate this question. Here, we compared the behavioral and endocrine response of male B. splendens to fights where there is no winner or loser by presenting them with a size-matched live interacting conspecific behind a transparent partition or with a mirror image. The aggressive response started with threat displays that were overall similar in frequency and duration towards both types of stimuli. Fights transitioned to overt attacks and interacting with a live conspecific elicited a higher frequency of attempted bites and head hits, as compared with the mirror image. There was a pronounced increase in plasma androgens (11-ketotestosterone and testosterone) and corticosteroids (cortisol) levels in response to the aggression challenge, independent of stimulus type. Post-fight intra-group levels of these hormones did not correlate with measures of physical activity or aggressive behavior. A linear discriminant analysis including all behavioral and endocrine data was a poor classifier of fish from the conspecific and mirror trials, showing that overall the behavioral and endocrine response to mirror images and conspecifics was similar. The results show that fight resolution is not necessary to induce an evident increase in peripheral levels of androgens and corticosteroids in B. splendens. However, the function of these hormones during present and future aggressive contests remains to be clarified.

Stress and immunity in poultry: light management and nanotechnology as effective immune enhancers to fight stress.

The poultry industry plays a significant role in boosting the economy of several countries, particularly developing countries, and acts as a good, cheap, and affordable source of animal protein. A stress-free environment is the main target in poultry production. There are several stressors, such as cold stress, heat stress, high stocking density, and diseases that can affect birds and cause several deleterious changes. Stress reduces feed intake and growth, as well as impairs immune response and function, resulting in high disease susceptibility. These effects are correlated with higher corticosteroid levels that modulate several immune pathways such as cytokine-cytokine receptor interaction and Toll-like receptor signaling along with induction of excessive production of reactive oxygen species (ROS) and thus oxidative stress. Several approaches have been considered to boost bird immunity to overcome stress-associated effects. Of these, dietary supplementation of certain nutrients and management modifications, such as light management, are commonly considered. Dietary supplementations improve bird immunity by improving the development of lymphoid tissues and triggering beneficial immune modulators and responses. Since nano-minerals have higher bioavailability compared to inorganic or organic forms, they are highly recommended to be included in the bird's diet during stress. Additionally, light management is considered a cheap and safe approach to control stress. Changing light from continuous to intermittent and using monochromatic light instead of the normal light improve bird performance and health. Such changes in light management are associated with a reduction of ROS production and increased antioxidant production. In this review, we discuss the impact of stress on the immune system of birds and the transcriptome of oxidative stress and immune-related genes, in addition, how nano-minerals supplementations and light system modulate or mitigate stress-associated effects.

Metabolic and nutritional condition of juvenile tiger sharks exposed to regional differences in coastal urbanization.

How varying levels of human activity, such as proximity and size of the nearest market (i.e., market gravity), influence the nutritional ecology and physiological condition of highly migratory marine predators is poorly understood. In the present study, we used a non-lethal approach to compare the concentration of metabolic hormones (i.e. corticosteroids and thyroid hormones) and plasma fatty acids between juvenile female tiger sharks (Galeocerdo cuvier) sampled in two areas of the subtropical north Atlantic, which differed markedly in their levels of coastal urbanization, Florida and the Bahamas (high versus low, respectively). We hypothesized that juvenile female tiger sharks sampled in water surrounding high coastal urbanization (Florida), would exhibit evidence of lower prey quality and higher energetic demands as compared to individuals sampled in relatively less urbanized areas of Northern Bahamas. Results revealed that relative corticosteroid levels (a proxy for energy mobilization) were higher in juvenile female tiger sharks sampled in Florida; however, no differences were found in concentrations of thyroid hormones (proxies of energetic adjustments) between the two locations. We found higher percentages of omega-3 polyunsaturated fatty acids (indicative of high prey quality) in juvenile tiger sharks from Florida, whereas higher percentages of bacterial markers (often indicative of domestic sewage effluent) were detected in the individuals sampled in the Bahamas. Taken together, these findings do not suggest that the differences in nutritional quality and metabolic condition found between the two sampling locations can be fully attributed to foraging in areas exposed to differing levels of urbanization. We speculate that these patterns may be due to the highly migratory nature and generalist feeding strategy of this species, even at the juvenile life stage, as well as proximity of sampling locations from shore.

Towards novel treatments for adrenal diseases: Cell- and gene therapy-based approaches

Adrenal insufficiency, the inability to produce adequate levels of corticosteroids, is a multi-causal disease that requires lifelong daily hormone replacement. Nevertheless, this cannot replace the physiological demand for steroids which are secreted following a circadian rhythm and vary in periods of stress; the consequences of under- or over-replacement include adrenal crisis and metabolic disturbances, respectively. Although clinical research has focused on enhancing the effectiveness/reducing side effects of current treatment modalities, only small improvements are deemed possible; thus, alternative solutions are urgently needed. Gene and cell therapy strategies have opened new possibilities for the cure of many diseases in a way that has never been possible before and could offer a viable option for the cure of adrenal diseases. The current state of cell- and gene-based approaches to restore adrenocortical function is discussed in this review.

Catabolic/Anabolic Imbalance Is Accompanied by Changes of Left Ventricular Steroid Nuclear Receptor Expression in Tachycardia-Induced Systolic Heart Failure in Male Pigs

BackgroundSteroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF. Methods and ResultsMale pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions. ConclusionsIn the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.

Extra-Adrenal Glucocorticoids and Mineralocorticoids Evidence for Local Synthesis in Various Organs

Glucocorticoids and mineralocorticoids are steroid chemicals traditionally thought to be discharged only by the adrenal organs. Nonetheless, ongoing proof has shown that corticosteroids can likewise be privately integrated in different tissues, including essential lymphoid organs, digestive system, skin, mind, and conceivably heart. Proof for nearby combination incorporates identification of steroidogenic chemicals and high neighborhood corticosteroid levels, even after adrenalectomy. Neighborhood union makes high corticosteroid fixations in extra-adrenal organs, now and again a lot higher than coursing focuses. Curiously, neighborhood corticosteroid blend can be controlled through privately communicated go betweens of the hypothalamic-pituitary-adrenal (HPA) hub or renin-angiotensin framework (RAS). In certain tissues (e.g., skin), these neighborhood control pathways may shape smaller than normal analogs of the pathways that direct adrenal corticosteroid creation.