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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.
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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3.
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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4.
The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers.
Mohammadi, AA, Jazayeri, S, Khosravi-Darani, K, Solati, Z, Mohammadpour, N, Asemi, Z, Adab, Z, Djalali, M, Tehrani-Doost, M, Hosseini, M, et al
Nutritional neuroscience. 2016;(9):387-395
Abstract
OBJECTIVE The aim of this study was to determine effects of probiotic yogurt and multispecies probiotic capsule supplementation on mental health and hypothalamic-pituitary-adrenal axis in petrochemical workers. METHODS The present randomized double-blind, placebo-controlled trial was conducted on 70 petrochemical workers. Subjects were randomly divided into three groups to receive 100 g/day probiotic yogurt + one placebo capsule (n = 25) or one probiotic capsule daily + 100 g/day conventional yogurt (n = 25) or 100 g/day conventional yogurt + one placebo capsule (n = 20) for 6 weeks. Mental health parameters including general health questionnaire (GHQ) and depression anxiety and stress scale (DASS) scores were measured. Fasting blood samples were obtained at the beginning and 6 weeks after the intervention to quantify hypothalamic-pituitary-adrenal axis. RESULTS After 6 weeks of intervention, a significant improvement of GHQ was observed in the probiotic yogurt (18.0 ± 1.5 vs. 13.5 ± 1.9, P = 0.007) and in the probiotic capsule group (16.9 ± 1.8 vs. 9.8 ± 1.9, P = 0.001), as well as a significant improvement in DASS scores in the probiotic yogurt (23.3 ± 3.7 vs. 13.0 ± 3.7, P = 0.02) and the probiotic capsule group (18.9 ± 3.2 vs. 9.4 ± 4.0, P = 0.006). However, there was no significant improvement in the conventional yogurt group (P = 0.05 for GHQ and P = 0.08 for DASS). DISCUSSION The consumption of probiotic yogurt or a multispecies probiotic capsule had beneficial effects on mental health parameters in petrochemical workers.
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5.
Effect of Early Parenteral Nutrition on the HPA Axis and on Treatment With Corticosteroids in Intensive Care Patients.
Meersseman, P, Boonen, E, Peeters, B, Vander Perre, S, Wouters, PJ, Langouche, L, Van den Berghe, G
The Journal of clinical endocrinology and metabolism. 2015;(7):2613-20
Abstract
BACKGROUND Nutrition can affect the hypothalamus-pituitary-adrenal axis. We hypothesized that early administration of parenteral nutrition (PN) during critical illness reduces plasma ACTH and cortisol concentrations and thereby increases the use of corticosteroids. METHODS This is a preplanned substudy of a randomized controlled trial (EPaNIC) that compared early PN with late PN in 4640 critically ill patients. We investigated the effect of early vs late PN on any steroid treatment and on treatment for ≥ 5 days to capture patients with clinical suspicion of adrenal insufficiency, and assessed whether this was related to an effect on septic shock. Also, in a propensity score-matched subgroup (n=174) of patients not receiving steroids, plasma ACTH and (free) cortisol were quantified. RESULTS Compared with late PN, more patients on early PN received treatment with corticosteroids (26.2% vs 23.8%; P = .05) and with corticosteroids for ≥ 5 days (14.0% vs 11.9%; P = .03). However, plasma ACTH and (free) cortisol concentrations were unaffected and thus could not explain the higher use of corticosteroids with early PN. Instead, more patients developed new septic shock with early PN (17.0%) than with late PN (14.2%) (P = .01). In multivariate logistic regression analysis, new septic shock was an independent determinant for ≥ 5 days steroid treatment (odds ratio, 6.25; 95% confidence interval, 4.93-7.94; P < .0001), statistically explaining the effect of early PN on steroid treatment. CONCLUSIONS Early PN did not affect plasma concentrations of ACTH and (free) cortisol, but increased the incidence of septic shock, which statistically explained why more patients on early PN received corticosteroids.
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6.
Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic-pituitary-adrenal axis: a randomized controlled study.
Habib, G, Jabbour, A, Artul, S, Hakim, G
Clinical rheumatology. 2014;(1):99-103
Abstract
The objective of this study was to evaluate the effect of intra-articular corticosteroid injection (IACI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal (HPA) axis in patients with osteoarthritis of the knee. Patients with symptomatic osteoarthritis of the knee who failed to respond to nonsteroidal anti-inflammatory medications and physical therapy were randomized between group 1 and group 2. Group 1 patients had an IACI of 80 mg of MPA at the knee joint and group 2 patients had an intra-articular injection (IAI) of 6 ml (60 mg) of sodium hyaluronate (control group). Immediately prior to the IAI and on weeks 1, 2, 3, 4, and 8 following IAI, patients from both groups underwent a low-dose (1 μg) adrenocorticotropin hormone (ACTH) stimulation test. Demographic, clinical, laboratory, and radiologic variables were documented in all patients. Both criteria of <7 μg/dl increase in the serum cortisol level and absolute levels of <18 μg/dl 30 min following the ACTH stimulation test were used to define secondary adrenal insufficiency (SAI). Twenty patients were randomized in each group. In group 1, 25 % of patients had SAI vs. none in group 2 (p = 0.0471). The earliest SAI was observed at week 2, and latest SAI was observed at week 4. SAI was observed at one time point, two consecutive time points, or two separate time points in the same patient. There was no correlation between SAI and any of the demographic, clinical, or laboratory variables. An IACI of 80 mg MPA at the knee joint induced a transient SAI in 25 % of the patients, an effect that was observed between week 2 and week 4 following the IACI.
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7.
Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial.
Saxton, JM, Scott, EJ, Daley, AJ, Woodroofe, M, Mutrie, N, Crank, H, Powers, HJ, Coleman, RE
Breast cancer research : BCR. 2014;(2):R39
Abstract
INTRODUCTION Many women experience emotional distress, depression and anxiety after a diagnosis of breast cancer. Psychological stress and depression have been associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation that may adversely affect immune system functioning and impact upon survival. This study investigated the effects of a lifestyle intervention on indices of psychological health status, HPA axis regulation and immune function in overweight women recovering from early-stage breast cancer treatment. METHODS A total of 85 women treated for breast cancer 3 to 18 months previously were randomly allocated to a 6-month exercise and hypocaloric healthy eating program plus usual care or usual care alone (control group). Women in the intervention group received three supervised exercise sessions per week and individualized dietary advice, supplemented by weekly nutrition seminars. Depressive symptoms (Beck Depression Inventory version II: BDI-II), perceived stress (Perceived Stress Scale: PSS), salivary diurnal cortisol rhythms; inflammatory cytokines (IL-6 and Tumor necrosis factor-α), leukocyte phenotype counts, natural killer (NK) cell cytotoxicity and lymphocyte proliferation following mitogenic stimulation were assessed at baseline and 6-month follow up. RESULTS Compared with the control group, the intervention group exhibited a reduction in depressive symptoms (adjusted mean difference, 95% confidence intervals (95% CI): -3.12, -1.03 to -5.26; P = 0.004) at the 6-month follow-up but no significant decrease in PSS scores (-2.07, -4.96 to 0.82; P = 0.16). The lifestyle intervention also had a significant impact on diurnal salivary cortisol rhythm compared with usual care alone, as evidenced by an increase in morning salivary cortisol at the 6-month follow-up (P <0.04), indicating a change in HPA axis regulation. Women in the control group had higher total leukocyte, neutrophil and lymphocyte counts in comparison to the intervention group at the 6-month follow-up (P ≤0.05), whereas there was no difference in NK cell counts (P = 0.46), NK cell cytotoxicity (P = 0.85) or lymphocyte proliferation responses (P = 0.11) between the two groups. CONCLUSION Our results show that the lifestyle intervention resulted in a reduction in depressive symptoms and a normalisation of HPA axis regulation. Such changes could have important implications for long-term survival in women recovering from early-breast cancer treatment. TRIAL REGISTRATION Current Controlled Trials: ISRCTN08045231.
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8.
Short- and long-term safety assessment of a two-compound ointment containing calcipotriene/betamethasone dipropionate (Taclonex/Daivobet/Dovobet ointment): hypothalamic-pituitary-adrenal axis function in patients with psoriasis vulgaris.
Fleming, C, Ganslandt, C, Leese, GP
Journal of drugs in dermatology : JDD. 2010;(8):969-74
Abstract
The two-compound ointment (Taclonex/Daivobet/Dovobet ointment) combining calcipotriene 50 microg/g and betamethasone 0.5 mg/g (as dipropionate) is very effective in the treatment of psoriasis vulgaris. There is a possibility that hypothalamo-pituitary-axis (HPA) suppression may occur if the potent corticosteroid component is absorbed to a sufficient extent. The effect of the two-compound ointment on HPA axis function was assessed in two studies. Study 1 was a four-week, double-blind study which compared the effects of the two-compound ointment with betamethasone 0.5 mg/g (as dipropionate; Diprosone) ointment in 24 patients with extensive psoriasis (involving 15-30% of the body surface area). No patients receiving the two-compound ointment had HPA axis suppression. Study 2 assessed HPA axis function after four and 52 weeks in a subset of patients (n = 19) participating in a long-term safety study. Patients were treated with the two-compound ointment for the first four weeks followed by 48 weeks of treatment as needed with either 1) two-compound ointment; 2) two-compound ointment alternating with calcipotriene four-weekly or 3) calcipotriene. No patients using the two-compound ointment for all 52 weeks or alternating four-weekly with calcipotriene had HPA axis suppression.
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9.
Early morning rise in hypothalamic-pituitary-adrenal activity: a role for maintaining the brain's energy balance.
Benedict, C, Kern, W, Schmid, SM, Schultes, B, Born, J, Hallschmid, M
Psychoneuroendocrinology. 2009;(3):455-62
Abstract
A profound rise in secretory activity in the early morning hours hallmarks the circadian regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. Functions and mechanisms underlying this regulation are barely understood. We tested the hypothesis that the early morning rise in HPA axis activity originates in part from a negative energy balance due to nocturnal fasting and concomitant increases in cerebral glucose demands. According to a 2x2 design, healthy men were infused with glucose (4.5mg/kgmin, 2300-0700h) and saline, respectively, during nocturnal sleep (n=9) or wakefulness (n=11). Circulating concentrations of ACTH, cortisol, glucose, insulin, and leptin were measured and food consumption in the next morning was assessed. Independent of sleep, glucose infusion reduced levels of ACTH (P<0.01) and cortisol (P<0.02) during the second night half. In the Sleep group, glucose infusion enhanced rapid eye movement (REM) sleep at the expense of sleep stage 2 (each P<0.05). Glucose infusion increased leptin levels in both groups (P<0.005) and reduced morning food intake in the Wake (P<0.02) but not in the Sleep group (P>0.46). Our findings support the view that increasing energy demands of the brain towards the end of the night essentially contribute to the early morning rise in HPA axis activity. Sleep is not critically involved in this glucose-glucocorticoid feedback loop but may reduce the brain's sensitivity to the anorexigenic effect of enhanced glucose supply.
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10.
Effects of rapid tryptophan depletion on salivary cortisol in older people recovered from depression, and the healthy elderly.
Porter, RJ, Gallagher, P, O'Brien, JT
Journal of psychopharmacology (Oxford, England). 2007;(1):71-5
Abstract
Reduced serotonin (5-HT) function and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the aetiology of major depression. We sought to examine this issue in the elderly by assessing the effects of lowering brain 5-HT on salivary and plasma cortisol in elderly patients who had recovered from at least one episode of major depression and in a healthy, age matched comparison group. A double-blind, cross-over design involving administration of two nutritionally balanced amino acid mixtures (with or without tryptophan) was used. Salivary cortisol was measured at intervals before and after the drink. There was no effect of acute tryptophan depletion (ATD) on salivary cortisol (ATD by time; F=0.97, df=7,210, p=0.454) but a significant interaction between group and time (F=3.91, df=7,210, p=0.010). Healthy subjects showed a marked increase in cortisol levels 2-3 hours into the procedure regardless of drink composition while recovered depressed subjects did not. In elderly patients who had recovered from depression there was no evidence of greater vulnerability of hypothalamic 5-HT pathways to 5-HT depletion. However, they demonstrated reduced reactivity of the HPA axis compared to healthy subjects.