An Introduction to Spiral Steroids

In addition to the classical steroids, which have cholesterol as a precursor, there are steroids with 7-dehydrocholesterol as a precursor. This review describes the identification of these steroids, their biosynthesis and some aspects of their function. There are three classes of these compounds, distinguished by the number of their carbon atoms, 23, 24 and 25. Each class has a spiral steroid and is a phosphodiester. Up until these investigations, no spiral steroids or steroid phosphodiesters were known. There are at least 13 compounds of which six have been purified to near homogeneity. Each one has been characterized by its mass and proposed composition. They function by regulating the NaK-ATPase. Based on the tissues in which they have been detected, each class of compound seems to regulate a different isoform of the NaK-ATPase. This is an important site of endocrine regulation.

The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance—study protocol for a randomized 4-way balanced cross-over trial

Background Asthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle. Methods The ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT. Summary/conclusions This clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals. Trial registration The trial is registered at the European Clinical Trials Database (Eudra CT) with the number: 2015-005598-19 as well as at the German register for clinical studies (DRKS number 00010574).

Tramadol Induced Ovarian and Uterine Changes in Albino Rats

Tramadol at the dose levels of 1mg and 3mg/100g body weight was administered to normal cycling rats for 20 days through intraperitoneal routes. At autopsy on 21st day significant reduction in the ovarian, uterine and body weight was observed. Histological observations showed decrease in the number and size of Graafian follicles, corpora lutea and increase in the atretic follicles in the ovary. The uterus showed absences of endometrial glands, decrease in the height of myometrium, endometrium and its epithelial cells. The total protein and glycogen content of the ovary and uterus is decreased whereas the cholesterol content is increased. The hypothalamo-hypophyseal gonadal axis is prominent regulator of reproductive activities in animals through neuro-endocrine regulation. In this study action of tramadol on ovary and uterine parameters is discussed.

Endocrine Regulation of Extra-skeletal Organs by Bone-derived Secreted Protein and the effect of Mechanical Stimulation

Bone serves as the support for body and provide attachment points for the muscles. The musculoskeletal system is the basis for the human body to complete exercise. Studies believe that bone is not only the basis for constructing structures, but also participates in the regulation of organs outside bone. The realization of this function is closely related to the protein secreted by bone. Whether bone can realize their positions in the human body is also related to their secretion. Bone-derived proteins provide a medium for the targeted regulation of bones on organs, making the role of bone in human body more profound and concrete. Mechanical stimulation effects the extra-skeletal organs by causing quantitative changes in bone-derived factors. When bone receives mechanical stimulation, the nichle of bone responds, and the secretion of various factors changes. However, whether the proteins secreted by bone can interfere with disease requires more research. In this review article, we will first introduce the important reasons and significance of the in-depth study on bone-derived secretory proteins, and summarize the locations, structures and functions of these proteins. These functions will not only focus on the bone metabolism process, but also be reflected in the cross-organ regulation. We specifically explain the role of typical bone-derived secretory factors such as osteocalcin (OCN), osteopontin (OPN), sclerostin (SOST) and fibroblast growth factor 23 (FGF23) in different organs and metabolic processes, then establishing the relationship between them and diseases. Finally, we will discuss whether exercise or mechanical stimulation can have a definite effect on bone-derived secretory factors. Understanding their important role in cross-organ regulation is of great significance for the treatment of diseases, especially for the elderly people with more than one basic disease.

Epigenetic Mechanisms of Endocrine-Disrupting Chemicals in Obesity

The incidence of obesity has dramatically increased over the last decades. Recently, there has been a growing interest in the possible association between the pandemics of obesity and some endocrine-disrupting chemicals (EDCs), termed “obesogens”. These are a heterogeneous group of exogenous compounds that can interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Oral intake, inhalation, and dermal absorption represent the major sources of human exposure to these EDCs. Recently, epigenetic changes such as the methylation of cytosine residues on DNA, post-translational modification of histones, and microRNA expression have been considered to act as an intermediary between deleterious effects of EDCs and obesity development in susceptible individuals. Specifically, EDCs exposure during early-life development can detrimentally affect individuals via inducing epigenetic modifications that can permanently change the epigenome in the germline, enabling changes to be transmitted to the next generations and predisposing them to a multitude of diseases. The purpose of this review is to analyze the epigenetic alterations putatively induced by chemical exposures and their ability to interfere with the control of energy metabolism and adipose tissue regulation, resulting in imbalances in the control of body weight, which can lead to obesity.

Endocrine disruptors in the pathogenesis of socially significant diseases such as diabetes mellitus, malignant neoplasms, cardiovascular diseases, pathology of the reproductive system

Some environmental chemicals capable of interfering with the endocrine regulation of energy metabolism and the structure of adipose tissue in the function of the reproductive, immune, cardiovascular and other systems are called endocrine disruptors or disruptors. According to the WHO definition, the term «endocrine disruptors» means: «Exogenous substances or mixtures thereof that alter the function (s) of the endocrine system and, as a result, cause adverse effects in the intact organism or in its offspring, or (sub) population.» This includes compounds to which humanity is exposed in daily life as a result of their use in pesticides, herbicides, industrial and household products, plastics, detergents, refractory impregnations and as ingredients in personal care products. This review will present the latest scientific data on various ERs, such as persistent organic pollutants (POPs): pesticides (mirex, chlordecane, endosulfan, hexachlorobenzene-HCB dichlorodiphenyltrichloroethane-DDT and its metabolites), industrial chemicals (bisphenol A, polybrominated ether -PBDE, polychlorinated biphenyls-PCB, nonylphenol, dioxins, perfluorooctanoic acid-PFOA, phthalates), pharmaceuticals (diethylstilbestrol-DES). ERs are regarded as compounds that cause obesity, since they have the ability to influence cellular processes associated with adipose tissue, initiating changes in lipid metabolism and adipogenesis. Analysis of scientific materials on this issue indicates that ERs are ubiquitous in the environment and have a detrimental effect on the health of animals and mankind. The scientific and practical interest in this article is based on the growing statistics of the development of such socially significant pathologies as obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, menstrual irregularities, as well as cancer and infertility, for of which obesity is a risk factor.

Insects as a New Complex Model in Hormonal Basis of Obesity

Nowadays, one of the biggest problems in healthcare is an obesity epidemic. Consumption of cheap and low-quality energy-rich diets, low physical activity, and sedentary work favor an increase in the number of obesity cases within many populations/nations. This is a burden on society, public health, and the economy with many deleterious consequences. Thus, studies concerning this disorder are extremely needed, including searching for new, effective, and fitting models. Obesity may be related, among other factors, to disrupting adipocytes activity, disturbance of metabolic homeostasis, dysregulation of hormonal balance, cardiovascular problems, or disorders in nutrition which may lead to death. Because of the high complexity of obesity, it is not easy to find an ideal model for its studies which will be suitable for genetic and physiological analysis including specification of different compounds’ (hormones, neuropeptides) functions, as well as for signaling pathways analysis. In recent times, in search of new models for human diseases there has been more and more attention paid to insects, especially in neuro-endocrine regulation. It seems that this group of animals might also be a new model for human obesity. There are many arguments that insects are a good, multidirectional, and complex model for this disease. For example, insect models can have similar conservative signaling pathways (e.g., JAK-STAT signaling pathway), the presence of similar hormonal axis (e.g., brain–gut axis), or occurrence of structural and functional homologues between neuropeptides (e.g., neuropeptide F and human neuropeptide Y, insulin-like peptides, and human insulin) compared to humans. Here we give a hint to use insects as a model for obesity that can be used in multiple ways: as a source of genetic and peptidomic data about etiology and development correlated with obesity occurrence as well as a model for novel hormonal-based drug activity and their impact on mechanism of disease occurrence.

Constraints and Opportunities for the Evolution of Metamorphic Organisms in a Changing Climate

We argue that developmental hormones facilitate the evolution of novel phenotypic innovations and timing of life history events by genetic accommodation. Within an individual’s life cycle, metamorphic hormones respond readily to environmental conditions and alter adult phenotypes. Across generations, the many effects of hormones can bias and at times constrain the evolution of traits during metamorphosis; yet, hormonal systems can overcome constraints through shifts in timing of, and acquisition of tissue specific responses to, endocrine regulation. Because of these actions of hormones, metamorphic hormones can shape the evolution of metamorphic organisms. We present a model called a developmental goblet, which provides a visual representation of how metamorphic organisms might evolve. In addition, because developmental hormones often respond to environmental changes, we discuss how endocrine regulation of postembryonic development may impact how organisms evolve in response to climate change. Thus, we propose that developmental hormones may provide a mechanistic link between climate change and organismal adaptation.

Drosophila as a Model for Microbiota Studies of Neurodegeneration

Accumulating evidence show that the gut microbiota is deeply involved not only in host nutrient metabolism but also in immune function, endocrine regulation, and chronic disease. In neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis, the gut-brain axis, the bidirectional interaction between the brain and the gut, provides new route of pathological spread and potential therapeutic targets. Although studies of gut microbiota have been conducted mainly in mice, mammalian gut microbiota is highly diverse, complex, and sensitive to environmental changes. Drosophila melanogaster, a fruit fly, has many advantages as a laboratory animal: short life cycle, numerous and genetically homogenous offspring, less ethical concerns, availability of many genetic models, and low maintenance costs. Drosophila has a simpler gut microbiota than mammals and can be made to remain sterile or to have standardized gut microbiota by simple established methods. Research on the microbiota of Drosophila has revealed new molecules that regulate the brain-gut axis, and it has been shown that dysbiosis of the fly microbiota worsens lifespan, motor function, and neurodegeneration in AD and PD models. The results shown in fly studies represents a fundamental part of the immune and proteomic process involving gut-microbiota interactions that are highly conserved. Even though the fly’s gut microbiota are not simple mimics of humans, flies are a valuable system to learn the molecular mechanisms of how the gut microbiota affect host health and behavior.