Epigenetics is the study of heritable changes in gene expression that occur without changes to the underlying DNA sequence. Epigenetic modifications can include DNA methylation, histone modifications, and non-coding RNAs, among others. These modifications can influence the expression of genes by altering the way DNA is packaged and accessed by transcriptional machinery, thereby affecting cellular function and behavior. Epigenetic modifications can be influenced by a variety of factors, including environmental exposures, lifestyle factors, and aging, whilst abnormal epigenetic modifications have been implicated in a range of diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. The study of epigenetics has the potential to provide new insights into the mechanisms of disease and could lead to the development of new diagnostic and therapeutic strategies. Exosomes can transfer epigenetic information to recipient cells, thereby influencing various physiological and pathological processes, and the identification of specific epigenetic modifications that are associated with a particular disease could lead to the development of targeted therapies that restore normal gene expression patterns. In recent years, the emerging role of exosomal epigenetics in human breast milk, highlighting its significance in infant nutrition and immune development. Milk exosomes are shown to carry epigenetic regulators, including miRNAs and long non-coding RNAs, which can modulate gene expression in recipient cells. These epigenetic modifications mediated by milk exosomal RNAs have implications for the development of the gastrointestinal tract, immune system, and metabolic processes in infants.
The second author acknowledges the support of the European Commission via the Horizon 2020 Grant No. 769129 PANOPTIS: Development of a Decision Support System for increasing the Resilience of Transportation Infrastructure based on combined use of terrestrial and airborne sensors and advanced modelling tools.
We describe the first case of an adrenocortical-pituitary hybrid tumor causing Cushing’s syndrome in a 17-yr-old boy. Adrenal vein sampling confirmed elevated secretion of both cortisol and ACTH precursors from a right adrenal mass, whereas pituitary ACTH levels, as determined by bilateral inferior petrosal sinus samples (IPSS), were unresponsive to CRH and equal to peripheral levels. There was no biochemical or histological evidence for a pheochromocytoma, but, rather, the tumor demonstrated lipid-rich clear cells characteristic of an adrenocortical adenoma. Immunohistochemical analysis revealed ACTH immunoreactivity and synaptophysin proteins in the tumor. Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PCR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells. Finally, ultrastructural analysis provided ultimate proof for adrenocortical-pituitary hybrid cells exhibiting the characteristic vesicular mitochondria and abundant smooth endoplasmic reticulum of steroid cells and the typical secretory granules of corticotrophs within the cytoplasm of the same cells. The adrenocortical tumor expressed the pituitary transcription factor pituitary homeobox factor 1 and the steroidogenic factor 1. The intermingling of the centrally located ectodermally derived pituitary tissue with the mesodermally derived adrenocortical tissue in this adenoma suggests a hitherto unrecognized genetic and phenotypic plasticity within the hypothalamic-pituitary-adrenal axis.
Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular atrophy, primary lateral sclerosis, and pseudobulbar palsy. Even though endocrine dysfunction independently impacts the ALS-related survival rate, the complex connection between ALS and the endocrine system has not been studied in depth. Here we review earlier and recent findings on how ALS interacts with hormones a) of the hypothalamus and pituitary gland, b) the thyroid gland, c) the pancreas, d) the adipose tissue, e) the parathyroid glands, f) the bones, g) the adrenal glands, and h) the gonads (ovaries and testes). Of note, endocrine issues should always be explored in patients with ALS, especially those with low skeletal muscle and bone mass, vitamin D deficiency, and decreased insulin sensitivity (diabetes mellitus). Because ALS is a progressively deteriorating disease, addressing any potential endocrine co-morbidities in patients with this malady is quite important for decreasing the overall ALS-associated disease burden. Importantly, as this burden is estimated to increase globally in the decades to follow, in part because of an increasingly aging population, it is high time for future multi-center, multi-ethnic studies to assess the link between ALS and the endocrine system in significantly larger patient populations. Last, the psychosocial stress experienced by patients with ALS and its psycho-neuro-endocrinological sequelae, including hypothalamic-pituitaryadrenal dysregulation, should become an area of intensive study in the future.
No abstract is provided for this article.
OBJECTIVE: To assess serum adiponectin levels of neonates in relation to ponderal index and birth length with and without adjustment for potential confounding factors including maternal factors and perinatal characteristics. DESIGN: A cross-sectional study. METHODS: Three hundred and three newborns (Caucasian, singleton, full term, with a birth weight of >/=2500 g, and apparently healthy) were included in the study. Blood samples were collected from the newborns no later than the fifth day of life for measurements of adiponectin and major IGF system components (IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3)). The data were analyzed using simple and multiple regression analyses. RESULTS: Adiponectin is substantially higher in neonates than in adults, with no evidence of the gender dimorphism observed among adults. We found an inverse association between neonatal adiponectin levels and newborn ponderal index and a positive association with newborn length by univariate analysis. We also found a statistically significant inverse association of adiponectin with jaundice/bilirubin, and a marginally significant positive association of this hormone with IGFBP-3 but no significant association with any maternal factors. In multivariate analysis, the inverse association between serum adiponectin and ponderal index does not remain significant after adjustment for potential confounding factors. In contrast, neonatal adiponectin levels correlate inversely significantly and independently with liver maturity and IGF-II and tend to remain positively associated with IGFBP-3 and increased birth length. CONCLUSIONS: An inverse association of adiponectin with ponderal index by univariate analysis is not independent from confounding factors. In contrast, the positive association between serum adiponectin and birth length may reflect either a direct effect of adiponectin or an adiponectin-mediated increase in the sensitivity of tissues to insulin and components of the IGF system, and needs to be explored further.
Finite-element models of varying sophistication may be employed to determine a building's seismic response with increasing complexity, potentially offering a higher fidelity at the cost of the computational load. To account for this effect on the reliability of performance assessment, model-type uncertainty needs to be incorporated as distinct to the uncertainty related to a given model's parameters. At present, only placeholder values are available in seismic guidelines. Instead, we attempt to quantify them accurately for a modern 20-story steel moment-resisting frame. Different types of three-dimensional (3D), two-dimensional (2D) multibay, and 2D single-bay multidegree-of-freedom models are investigated, together with their equivalent single-degree-of-freedom ones, to evaluate the model dependency of the response both within each broad model category, as well as among different categories. In conclusion, ensemble values are recommended for the uncertainty in each model category showing that for the perfectly-symmetric perimeter-frame P-Δ sensitive building under investigation, the uncertainty stemming from 3D versus 2D or distributed versus lumped plasticity models is lower than the governing record-to-record variability.
Abstract: Pathologic stress (distress) disturbs immune, cardiovascular, metabolic, and behavioral homeostasis. Individuals living with HIV and those at risk are vulnerable to stress disorders. Corticotropin-releasing hormone (CRH) is critical in neuroendocrine immune regulation. CRH, a neuropeptide, is distributed in the central and peripheral nervous systems and acts principally on CRH receptor type 1 (CRHR1). CRH in the brain modulates neuropsychiatric disorders. CRH and stress modulation of immunity is two-pronged; there is a direct action on hypothalamic–pituitary–adrenal secretion of glucocorticoids and through immune organ sympathetic innervation. CRH is a central and systemic proinflammatory cytokine. Glucocorticoids and their receptors have gene regulatory actions on viral replication and cause central and systemic immune suppression. CRH and stress activation contributes to central nervous system (CNS) viral entry important in HIV-associated neurocognitive disorders and HIV-associated dementia. CNS CRH overproduction short-circuits reward, executive, and emotional control, leading to addiction, cognitive impairment, and psychiatric comorbidity. CRHR1 is an important therapeutic target for medication development. CRHR1 antagonist clinical trials have focused on psychiatric disorders with little attention paid to neuroendocrine immune disorders. Studies of those with HIV and those at risk show that concurrent stress-related disorders contribute to higher morbidity and mortality; stress-related conditions, addiction, immune dysfunction, and comorbid psychiatric illness all increase HIV transmission. Neuropsychiatric disease, chronic inflammation, and substance abuse are endemic, and chronic distress is a pathologic factor. It is being understood that stress and CRH are fundamental to neuroendocrine immunity; therapeutic interventions with existing and novel agents hold promise for restoring homeostasis, reducing morbidity and mortality for those with HIV and possibly reducing future disease transmission. Keywords: corticotropin-releasing hormone, stress, neuroendocrine immunology, hypothalamic–pituitary–adrenal, cytokine, glucocorticoid resistance
Journal Article Abnormal Pituitary-Adrenal Responses to Corticotropin-Releasing Hormone in Patients with Seasonal Affective Disorder: Clinical and Pathophysiological Implications Get access JEAN R. JOSEPH-VANDERPOOL, JEAN R. JOSEPH-VANDERPOOL 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar NORMAN E. ROSENTHAL, NORMAN E. ROSENTHAL 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar GEORGE P. CHROUSOS, GEORGE P. CHROUSOS 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar THOMAS A. WEHR, THOMAS A. WEHR 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar ROBERT SKWERER, ROBERT SKWERER 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar SIEGFRIED KASPER, SIEGFRIED KASPER 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar PHILIP W. GOLD PHILIP W. GOLD 1Clinical Psychobiobgy Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20009 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Clinical Endocrinology & Metabolism, Volume 72, Issue 6, 1 June 1991, Pages 1382–1387, https://doi.org/10.1210/jcem-72-6-1382 Published: 01 June 1991 Article history Received: 02 January 1990 Published: 01 June 1991
The human hypothalamus lies ventrally to the thalamus and extends from the rostral part of the optic chiasm to the caudal edge of the mamillary bodies. It originates in the alar plate of diencephalon, its sulcus becoming identifiable by the 5th wk of gestation. The hypothalamus is a highly complex organ coordinating central nervous system (CNS) centers and neuroendocrine, metabolic, autonomic nervous and behavioral functions. A system of nerve fibers and portal vessels connects the hypothalamus to the pituitary. The axon terminals of neurons originating in several hypothalamic nuclei, including the supraoptic, the paraventricular, the arcuate, and the ventromedial nucleus, form the median eminence located rostrally to the mamillary bodies. The median eminence communicates with the anterior pituitary via a local portai venous System, which permits the direct hematogenous communication between neurons and endocrine cells. The hypothalamic neurons regulating the function of anterior pituitary corticotrophs are located in the parvocellular part of the paraventricular hypothalamic nucleus. They synthesize the neuropeptides corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP), which, packaged in secretory vesicles, travel the neural axons and reach the median eminence, where they are placed in specifie secretory areas beneath the subplasmalemal actin network ready to be secreted into the portai System.
