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"Endocrine glands."
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Learning about the endocrine and reproductive systems
\"Learn how these two wonderful systems work together to ensure the survival of the human race and discover some amazing facts about them both\"-- Provided by publisher.
Book
Long-Term Endocrine and Metabolic Consequences of Cancer Treatment: A Systematic Review
Abstract
The number of patients surviving ≥5 years after initial cancer diagnosis has significantly increased during the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is that the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified, including radiation, sex, and age at the time of diagnosis. A systematic literature search has been conducted using the PubMed database to offer a detailed overview of the spectrum of late endocrine disorders following oncological treatment. Most data are based on late effects of treatment in former childhood cancer patients for whom specific guidelines and recommendations already exist, whereas current knowledge concerning late effects in adult-onset cancer survivors is much less clear. Endocrine sequelae of cancer therapy include functional alterations in hypothalamic-pituitary, thyroid, parathyroid, adrenal, and gonadal regulation as well as bone and metabolic complications. Surgery, radiotherapy, chemotherapy, and immunotherapy all contribute to these sequelae. Following irradiation, endocrine organs such as the thyroid are also at risk for subsequent malignancies. Although diagnosis and management of functional and neoplastic long-term consequences of cancer therapy are comparable to other causes of endocrine disorders, cancer survivors need individually structured follow-up care in specialized surveillance centers to improve care for this rapidly growing group of patients.
Journal Article
Organotypic vasculature
Blood vessels have long been considered as passive conduits for blood and circulating cells that, at best, respond to exogenous cytokines. However, recent work has shown that blood vessels serve as a highly dynamic interface between the circulation and tissues. Augustin et al. review molecular mechanisms of vascular development and function in different organs. Differentiated endothelial cells develop as a sort of cobblestone monolayer to form one of the largest surfaces within the body. Vascular control of the tissue microenvironment is vital, not only for normal tissue development and homeostasis, but also for disease states ranging from inflammation to cancer. Science , this issue p. eaal2379 Blood vessels form one of the body’s largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed–specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function.
Journal Article
The adrenal reset diet : strategically cycle carbs and proteins to lose weight, balance hormones, and move from stressed to thriving
\"The Adrenal Reset Diet is the first scientifically sound, patient-tested weight-loss plan developed by a natural endocrinologist, Dr. Alan Christianson. He heals readers in any of the three stages of adrenal impairment--Stressed, Wired and Tired, or Crashed. Readers learn their stage and receive distinct strategies for diet, activity, and lifestyle change to bring them to Thriving. Recent study participants halved their cortisol levels in just 30 days--and lost an average of 9 pounds!\"-- Provided by publisher.
Book
Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk
Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.
Journal Article
Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues
Background
Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.
Methods
We compared
ACE2
expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s
t
test. We also investigated the correlations between
ACE2
expression and immune signatures in various tissues using Pearson’s correlation test.
Results
ACE2
expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle.
ACE2
showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland.
ACE2
was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels,
ACE2
expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs,
ACE2
expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.
Conclusions
Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
Journal Article
A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks
Stress activates a complex network of hormones known as the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is dysregulated in chronic stress and psychiatric disorders, but the origin of this dysregulation is unclear and cannot be explained by current HPA models. To address this, we developed a mathematical model for the HPA axis that incorporates changes in the total functional mass of the HPA hormone‐secreting glands. The mass changes are caused by HPA hormones which act as growth factors for the glands in the axis. We find that the HPA axis shows the property of dynamical compensation, where gland masses adjust over weeks to buffer variation in physiological parameters. These mass changes explain the experimental findings on dysregulation of cortisol and ACTH dynamics in alcoholism, anorexia, and postpartum. Dysregulation occurs for a wide range of parameters and is exacerbated by impaired glucocorticoid receptor (GR) feedback, providing an explanation for the implication of GR in mood disorders. These findings suggest that gland‐mass dynamics may play an important role in the pathophysiology of stress‐related disorders.
Synopsis
Prolonged activation of the HPA axis leads to dysregulation and has clinical consequences. This study presents a mechanism for HPA dysregulation based on the effect of HPA hormones acting as growth factors for their downstream glands.
A mathematical model that includes gland functional mass dynamics introduces a new slow timescale of weeks to the HPA axis.
The gland masses grow during prolonged activation, providing dynamical compensation, and recover with overshoots over weeks after withdrawal of activation.
These overshoots explain the observed HPA dysregulation in pathological conditions, and clarify the role of glucocorticoid receptors in resilience to prolonged stress.
Graphical Abstract
Prolonged activation of the HPA axis leads to dysregulation and has clinical consequences. This study presents a mechanism for HPA dysregulation based on the effect of HPA hormones acting as growth factors for their downstream glands.
Journal Article
Genome-wide association study of body fat distribution identifies adiposity loci and sex-specific genetic effects
Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested to be more pathogenic compared to fat stored in other compartments. In this study, we perform genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. 98 independent associations with body fat distribution are identified, 29 that have not previously been associated with anthropometric traits. A high degree of sex-heterogeneity is observed and the effects of 37 associated variants are stronger in females compared to males. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling.
Obesity and the distribution of fat within the body are risk factors for cardiometabolic diseases. Here, Rask-Andersen et al. perform GWAS for bio-electrical impedance measurements in UK Biobank participants and identify 29 novel independent loci for fat distribution and a high degree of sex-heterogeneity.
Journal Article
Circulating non-coding RNA biomarkers of endocrine tumours
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies.
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. This Review outlines ncRNA biology, before discussing research findings on ncRNAs in endocrine tumours and their potential utility as biomarkers, ending with an outlook for future studies.
Key points
Endocrine tumours, including pituitary, pancreatic and parathyroid neuroendocrine tumours, adrenocortical cancer and phaeochromocytoma–paraganglioma, share common features in their pathogenesis, genetic background and associated clinical challenges.
Non-coding RNAs (ncRNAs) can be exploited as tissue-specific biomarkers of malignancy, prognosis and follow-up, and their circulating counterparts can be measured in blood samples as a form of liquid biopsy.
Circulating microRNAs show promising utility as biomarkers of malignancy and prognosis in adrenocortical tumours, and several other differentially expressed ncRNAs were reported in other endocrine tumours.
Apart from circulating
miR-483-5p
and
miR-143-3p
, few overlaps are observed in the circulating ncRNA molecules expressed from different types of endocrine tumour.
None of these biomarkers has yet been introduced into clinical practice, which is mainly owing to difficulties in standardization and methodology.
Journal Article