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1.
ABCC1 modulates negative feedback control of the hypothalamic-pituitary-adrenal axis in vivo in humans.
Kyle, CJ, Nixon, M, Homer, NZM, Morgan, RA, Andrew, R, Stimson, RH, Walker, BR
Metabolism: clinical and experimental. 2022;:155118
Abstract
BACKGROUND Cortisol and corticosterone both circulate in human plasma and, due to differing export by ATP-binding cassette (ABC) transporters, may exert differential cellular effects. ABCB1 (expressed in brain) exports cortisol not corticosterone while ABCC1 (expressed in adipose and skeletal muscle) exports corticosterone not cortisol. We hypothesised that ABCC1 inhibition increases corticosteroid receptor occupancy by corticosterone but not cortisol in humans. METHODS A randomised double-blind crossover study was conducted in 14 healthy men comparing placebo and ABCC1 inhibitor probenecid. Blood sampling, including from veins draining adipose and muscle, was undertaken before and after administration of mineralocorticoid receptor antagonist potassium canrenoate and glucocorticoid receptor antagonist mifepristone (RU486). RESULTS During placebo, systemic plasma cortisol and corticosterone concentrations increased promptly after canrenoate. Cortisol uptake was detected from adipose but not muscle following canrenoate + RU486. Probenecid significantly increased systemic cortisol concentrations, and tended to increase corticosterone and ACTH concentrations, after combined receptor antagonism but had no effects on net glucocorticoid balance in either adipose or muscle. Using quantitative PCR in brain bank tissue, ABCC1 expression was 5-fold higher in human pituitary than hypothalamus and hippocampus. ABCB1 was more highly expressed in hypothalamus compared to pituitary. CONCLUSIONS Although displacement of corticosterone and/or cortisol from receptors in adipose and skeletal muscle could not be measured with sufficient precision to detect effects of probenecid, ABCC1 inhibition induced a greater incremental activation of the hypothalamic-pituitary-adrenal axis after combined receptor blockade, consistent with ABCC1 exporting corticosterone from the pituitary and adding to the evidence that ABC transporters modulate tissue glucocorticoid sensitivity.
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2.
Psychosocial Stress and Mechanisms of Skin Health: A Comprehensive Update.
Sun, MD, Rieder, EA
Journal of drugs in dermatology : JDD. 2021;(1):62-69
Abstract
Although the relationship between psychosocial stress and skin health is commonly invoked in both the scientific and popular literature, its underlying mechanisms are still not well understood. In this review, we provide a comprehensive update on the pathophysiology of stress and its clinical impact on skin homeostasis. The recent characterization of a bidirectional HPA stress axis in the skin has illuminated peripheral stress pathways, with effects spanning inflammation, atopy, barrier function, dermal thinning, wound healing, and melanogenesis. Additionally, new research into the cutaneous microbiome suggests the development of stress-induced dysbiosis through the “gut-brain-skin” axis. These new findings help contextualize how lifestyle factors such as diet, personal care practices, and sleep patterns may mediate and sometimes amplify the cutaneous impacts of psychological stress. We aim to clarify these clinically important relationships and highlight areas of future study that have widespread academic, clinical, and commercial implications. J Drugs Dermatol. 2021;20(1):62-29. doi:10.36849/JDD.5608.
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3.
Deciphering the Association Between Hypothalamus-Pituitary-Adrenal Axis Activity and Obesity: A Meta-Analysis.
Ostinelli, G, Scovronec, A, Iceta, S, Ouellette, AS, Lemieux, S, Biertho, L, Bégin, C, Michaud, A, Tchernof, A
Obesity (Silver Spring, Md.). 2021;(5):846-858
Abstract
OBJECTIVE Both the cortisol awakening response (CAR; corresponding to the state measurement) and hair cortisol concentration (HCC; corresponding to the trait measurement) are considered reliable markers of hypothalamus-pituitary-adrenal axis activity. Because cortisol has long been associated with adiposity, this systematic review and meta-analysis aims to summarize and compare the literature around CAR and HCC and their association with obesity or fat distribution indices. METHODS The PubMed, Web of Science (Web of Science Core Collection and Medline), EBSCO Information Services, Embase, and PsycNET databases were searched, and full-text articles investigating the association between CAR or HCC and markers of adiposity in humans were included. Meta-analyses were then performed to compare studies associating CAR or HCC with BMI (a marker of general adiposity) and waist circumference (a marker of fat distribution). RESULTS The results of this review highlight inconsistencies in cortisol sampling and CAR computation, which makes comparisons between studies difficult. It was found that adiposity indices are not associated with CAR but that they correlate significantly and positively with HCC. The subgroup analysis hinted to possible age differences in the magnitude of the association between HCC and BMI. CONCLUSIONS Trait rather than state measurement of the hypothalamus-pituitary-adrenal axis activity is associated with increased general and abdominal adiposity in humans.
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4.
The calming effect of roasted coffee aroma in patients undergoing dental procedures.
Pachimsawat, P, Tangprasert, K, Jantaratnotai, N
Scientific reports. 2021;(1):1384
Abstract
Coffee beverage consumption is well-known to exert various health benefits; however, the effects of coffee aroma are rarely explored. This study aimed to investigate the calming effect of inhaling coffee aroma while the patients underwent dental procedures (probing and scaling). Salivary α-amylase (sAA) and cortisol (sCort) levels were measured as proxies of sympathetic nervous system and hypothalamic-pituitary-adrenal axis responses to stress respectively. Blood pressures and pulse rates were recorded. The results showed that undergoing dental procedures could increase sAA and sCort levels of the patients inhaling sham aroma while those inhaling coffee aroma had significantly decreased sAA and sCort levels (40% and 25% differences, respectively). The pulse rates of those inhaling coffee aroma were also lower. Subjective assessment using visual analog scale was in line with objective measures as well. The preference for coffee aroma or the frequency of coffee drinking had no effect on the sAA and sCort responses. This is the first study to provide evidence on the effect of coffee aroma on sAA and sCort levels in patients undergoing dental procedures.
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5.
Dysregulation of the Hypothalamic-Pituitary-Testicular Axis due to Energy Deficit.
Grossmann, M, Wittert, GA
The Journal of clinical endocrinology and metabolism. 2021;(12):e4861-e4871
Abstract
CONTEXT Although gonadal axis dysregulation from energy deficit is well recognized in women, the effects of energy deficit on the male gonadal axis have received much less attention. EVIDENCE ACQUISITION To identify relevant articles, we conducted PubMed searches from inception to May 2021. EVIDENCE SYNTHESIS Case series and mechanistic studies demonstrate that energy deficit (both acutely over days or chronically over months) either from inadequate energy intake and/or excessive energy expenditure can lower serum testosterone concentration as a result of hypothalamic-pituitary-testicular (HPT) axis dysregulation in men. The extent to which this has clinical consequences that can be disentangled from the effects of nutritional insufficiency, concomitant endocrine dysregulation (eg, adrenal and thyroid axis), and coexisting comorbidities (eg, depression and substance abuse) is uncertain. HPT axis dysfunction is primarily the result of loss of GnRH pulsatility resulting from a failure of leptin to induce kisspeptin signaling. The roles of neuroendocrine consequences of depression, hypothalamic-pituitary-adrenal axis activation, proinflammatory cytokines, Ghrelin, and genetic susceptibility remain unclear. In contrast to hypogonadism from organic pathology of the HPT axis, energy deficit-associated HPT dysregulation is functional, and generally reversible by restoring energy balance. CONCLUSIONS The clinical management of such men should aim to restore adequate nutrition and achieve and maintain a healthy body weight. Psychosocial comorbidities must be identified and addressed. There is no evidence that testosterone treatment is beneficial. Many knowledge gaps regarding epidemiology, pathophysiology, and treatment remain and we highlight several areas that require future research.
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6.
Reproductive health in women with type 2 diabetes mellitus.
Creţu, D, Cernea, S, Onea, CR, Pop, RM
Hormones (Athens, Greece). 2020;(3):291-300
Abstract
As type 2 diabetes mellitus (T2DM) reaches epidemic proportions in the developed world and the age at diagnosis decreases, more women of reproductive age are being affected. In this article, we provide a synoptic view on potential mechanisms and relevant factors underlying menstrual cycle disorders and fertility issues in women with T2DM. The article discusses the function of the hypothalamic-pituitary-ovarian (HPO) axis, the central role of the hypothalamus in the homeostasis of this system, the central modulators of the axis, and the peripheral metabolic signals involved in neuroendocrine control of reproduction. The available literature on the relationship between T2DM and the female reproductive lifespan, menstrual cycle disorders, fertility issues, and gestational health in women with T2DM are also discussed. The data so far indicate that there is a "U-shaped" relationship between menarche, menopause, and T2DM, both early and late menarche/menopause being risk factors for T2DM. Hyperglycemia and its consequences may be responsible for the effects of T2DM on reproductive health in women, but the exact mechanisms are not as yet fully understood; thus, more studies are needed in order to identify factors causing disruption of the HPO axis.
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7.
The causes of adverse changes of testosterone levels in men.
Wrzosek, M, Woźniak, J, Włodarek, D
Expert review of endocrinology & metabolism. 2020;(5):355-362
Abstract
INTRODUCTION As men age, progressive testosterone deficiency syndrome becomes an increasingly common problem. However, the decreased testosterone levels are not only the result of advanced age. AREAS COVERED PubMed search of published data on testosterone, nutritional deficiency, stress, sleep, and obesity. Many factors impact the male HPG axis (the hypothalamic-pituitary-adrenal), including body weight, calorific and nutritional value of a diet, the amount and quality of sleep, as well as the level of stress. In the case of persons of healthy weight, a below-average calorific value of a diet may decrease the levels of testosterone in men. On the other hand, the same caloric deficiency in obese persons may result in a neutral or positive impact on testosterone levels. EXPERT OPINION Many factors, including external, environmental and internal factors, influence testosterone levels. Undoubtedly, nutritional deficiency, and particularly of such nutrients as zinc, magnesium, vitamin D, together with low polyphenols intake, affects the HPG axis. The levels of mental and oxidative stress can also adversely impact the axis. Hence, a diagnosis of the cause of disturbance in testosterone levels depends on many factors and requires a broad range of research, as well as a change of patients' lifestyle.
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8.
Short-Term d-Aspartic Acid Supplementation Does Not Affect Serum Biomarkers Associated With the Hypothalamic-Pituitary-Gonadal Axis in Male Climbers.
Crewther, B, Witek, K, Draga, P, Zmijewski, P, Obmiński, Z
International journal of sport nutrition and exercise metabolism. 2019;(3):259-264
Abstract
D-aspartic acid (DAA) is promoted as a testosterone (T) enhancing supplement by mechanisms involving the hypothalamic-pituitary-gonadal (HPG) axis. Here, we investigated the short-term effects of DAA on serum biomarkers of the HPG-axis in male climbers. Using a single-blinded, placebo-controlled design, 16 climbers were randomly assigned to either a DAA (3 g/day) or placebo (3 g/day) supplement for 2 weeks. The reverse treatment commenced after a 2-week washout, with all conditions administered in a balanced manner. The subjects maintained their normal weekly training across this study. Serum samples taken before and after each treatment were analyzed for T, luteinizing hormone, sex hormone binding globulin, and cortisol (C), and free T was calculated (cFT). The DAA supplement did not significantly affect serum T, cFT, and luteinizing hormone levels. Only a main effect of time on sex hormone binding globulin (6.8% increase) and C (13.6% decrease) emerged (p < .03). Significant negative associations were identified between pretest values and changes (%) in T, cFT, luteinizing hormone, and C levels with DAA and/or placebo, but these relationships did not differ between treatments (p > .46). Additional measures of physical function and serum hematology also failed to respond to DAA. In summary, a daily dose of DAA during a short training period did not influence T and selected indicators of the HPG-axis in male climbers. Other parameters linked to athletic performance and health status were also unaffected. Our findings support evidence showing that DAA (including DAA-blended supplements) at either recommended or higher dosages does not afford any ergogenic benefits for athletic males.
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9.
Female Reproductive, Adrenal, and Metabolic Changes during an Antarctic Traverse.
Gifford, RM, O'Leary, T, Cobb, R, Blackadder-Weinstein, J, Double, R, Wardle, SL, Anderson, RA, Thake, CD, Hattersley, J, Imray, CHE, et al
Medicine and science in sports and exercise. 2019;(3):556-567
Abstract
PURPOSE To explore the effects of the first all-female transantarctic expedition on hormonal axes pertinent to reproductive and metabolic function. METHODS Six females (age, 28-36 yr; body mass index, 24.2 ± 0.97 kg·m) hauled 80-kg sledges 1700 km in 61 d. Estimated average energy intake was 20.8 ± 0.1 MJ·d (4970 ± 25 kcal·d). Whole and regional body composition was measured by dual-energy x-ray absorptiometry 1 and 2 months before and 15 d after, the expedition. Body fat was also estimated by skinfold and bioimpedance immediately before and after the expedition. Basal metabolic and endocrine blood markers and, after 0.25 mg dexamethasone suppression, 1-h 10-μg gonadorelin and 1.0 μg adrenocortiocotrophin-(1-24) tests were completed, 39-38 d preexpedition and 4 to 5 d and 15 to 16 d postexpedition. Cortisol was assessed in hair (monthly average concentrations) and saliva (five-point day curves and two-point diurnal sampling). RESULTS Average body mass loss was 9.37 ± 2.31 kg (P < 0.0001), comprising fat mass only; total lean mass was maintained. Basal sex steroids, corticosteroids, and metabolic markers were largely unaffected by the expedition except leptin, which decreased during the expedition and recovered after 15 d, a proportionately greater change than body fat. Luteinizing hormone reactivity was suppressed before and during the expedition, but recovered after 15 d, whereas follicle-stimulating hormone did not change during or after the expedition. Cortisol reactivity did not change during or after the expedition. Basal (suppressed) cortisol was 73.25 ± 45.23 mmol·L before, 61.66 ± 33.11 mmol·L 5 d postexpedition and 54.43 ± 28.60 mmol·L 16 d postexpedition (P = 0.7). Hair cortisol was elevated during the expedition. CONCLUSIONS Maintenance of reproductive and hypothalamic-pituitary-adrenal axis function in women after an extreme physical endeavor, despite energy deficiency, suggests high female biological capacity for extreme endurance exercise.
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10.
Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review.
Wang, J, Maxwell, CA, Yu, F
Biological research for nursing. 2019;(1):80-106
Abstract
The objectives of this literature review were to (1) synthesize biological processes linked to frailty and their corresponding biomarkers and (2) identify potential associations among these processes and biomarkers. In September 2016, PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and Embase were searched. Studies examining biological processes related to frailty in older adults (≥60 years) were included. Studies were excluded if they did not employ specific measures of frailty, did not report the association between biomarkers and frailty, or focused on nonelderly samples (average age < 60). Review articles, commentaries, editorials, and non-English articles were also excluded. Fifty-two articles were reviewed, reporting six biological processes related to frailty and multiple associated biomarkers. The processes (biomarkers) include brain changes (neurotrophic factor, gray matter volume), endocrine dysregulation (growth hormones [insulin-like growth factor-1 and binding proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid function, reproductive axis, and hypothalamic-pituitary-adrenal axis), enhanced inflammation (C-reactive protein, interleukin-6), immune dysfunction (neutrophils, monocytes, neopterin, CD8+CD28-T cells, albumin), metabolic imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end products), and oxidative stress (antioxidants, telomere length, glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist within and between these processes. Biomarkers were associated with frailty in varied strengths, and the causality remains unclear. In conclusion, frailty is related to multisystem physiological changes. Future research should examine the dynamic interactions among these processes to inform causality of frailty. Given the multifactorial nature of frailty, a composite index of multisystem biomarkers would likely be more informative than single biomarkers in early detection of frailty.