Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function

1995 ◽  
Vol 144 (2) ◽  
pp. 301-310 ◽  
Author(s):  
U Knutsson ◽  
P Stierna ◽  
C Marcus ◽  
J Carlstedt-Duke ◽  
K Carlström ◽  
...  

Abstract Glucocorticoids are among the most potent anti-inflammatory agents that can be used in the treatment of rhinitis. Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids. In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks. Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay. Serum cortisol, osteocalcin and urinary cortisol levels were also determined. An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response. In peripheral lymphocytes, GR mRNA levels were significantly down-regulated. MTIIa mRNA levels increased significantly. Serum osteocalcin decreased significantly during treatment with both BUD and FP. Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment. In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes. These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact. Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids. Journal of Endocrinology (1995) 144, 301–310

2011 ◽  
Vol 210 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Petra Popovics ◽  
Zoltan Rekasi ◽  
Alan J Stewart ◽  
Magdolna Kovacs

Pituitary inhibin B, activin B, and follistatin are local regulators of FSH. Activin B is a homodimeric molecule (βB–βB), while inhibin B contains an α and a βB subunit. The regulation of gene expression of α, βB, and follistatin by local and endocrine hormones was examined in pituitaries from female rats and in perifused pituitary cells by RT-PCR. Ovariectomy (OVX) induced an elevation in the mRNA level of α and βB subunits and follistatin. Short-term (4 h) treatment of pituitary cells with GnRH decreased both the inhibin α and the inhibin/activin βB subunit mRNA levels, while long-term treatment (20 h) with 100 nM GnRH stimulated the expression of both subunits. In contrast, the mRNA level of follistatin was elevated after the short-term GnRH treatment. Long-term exposure of pituitary cells to estradiol and inhibin B suppressed the mRNA expression of βB and had no effect on the expression of α subunit and follistatin. Our results demonstrate that the increased expressions of inhibin/activin subunits and follistatin in the post-OVX period can be induced by the lack of gonadal negative feedback, resulting in a high GnRH environment in the pituitary. This study reports for the first time that GnRH administered in high doses and for a long period stimulates the gene expression of inhibin/activin subunits and thereby may contribute to the stimulatory effect of OVX on the expression of these genes.


1995 ◽  
Vol 145 (3) ◽  
pp. 455-460 ◽  
Author(s):  
A C McFarlane ◽  
S Potocnik ◽  
M Towstoless ◽  
K Moritz ◽  
E M Wintour

Abstract Pituitary-adrenal responses to intravenous infusion of ovine corticotrophin-releasing hormone (oCRH) or arginine vasopressin (AVP) and to haemorrhage were examined in the ovine foetus prior to 90 days of gestation (term 145–150 days). In chronically cannulated foetuses (n=8), between 74 and 84 days of gestation, basal ACTH levels were less than 20 pg/ml while cortisol levels were 6·5 ± 1·5 nmol/l (mean±s.e m.). Intravenous infusion of oCRH (1 μg/h for 60 min) or AVP (1 μg/h for 60 min) significantly increased ACTH (P<0·05 for both treatments) and cortisol (P<0·01 for both treatments) levels, although the response to both hormones was modest. In acutely studied foetuses of a similar age (70–90 days of gestation, mean 82·0 ± 1·4 days, n=7), exteriorization and progressive haemorrhage significantly (P<0·05) elevated ACTH levels from 117·4 ± 32·1 pg/ml to a maximal value of 329·2 ± 112·8 pg/ml, the maximal ACTH response corresponding to the removal of a volume of blood equivalent to 6·6 ±1·2% of the pre-haemorrhage body weight. The present study has demonstrated that the ovine foetal pituitary, in vivo, is responsive to exogenous and endogenous stimuli by mid-gestation and, at this age, although basal cortisol levels are low, the foetal adrenal is capable of responding to elevated ACTH levels in the short term. Journal of Endocrinology (1995) 145, 455–460


2007 ◽  
Vol 51 (7) ◽  
pp. 1110-1117 ◽  
Author(s):  
Silvia R. Correa-Silva ◽  
Sérgio O. Nascif ◽  
Marcos R. Silva ◽  
Patrícia Molica ◽  
Ana-Maria J. Lengyel

GH responses to ghrelin, GHRP-6, and GHRH in Cushing’s disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (mg/L; mean ± SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 ± 4.5; 3.8 ± 1.6, and 0.6 ± 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75%), but GH responses did not change (7.0 ± 2.0; 3.1 ± 0.8; 0.9 ± 0.2, respectively). After treatment, there was a significant reduction in cortisol (mg/dL) responses to ghrelin (before: 30.6 ± 5.2; after: 24.2 ± 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 ± 69.9; GHRP-6: 199.8 ± 88.8) and after treatment (ghrelin: 159.7 ± 40.3; GHRP-6: 227 ± 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.


Author(s):  
Ga-Young Lim ◽  
Tae-Won Jang ◽  
Chang-Sun Sim ◽  
Yeon Soon Ahn ◽  
Kyoung Sook Jeong

(1) Study Objectives: By investigating the change of cortisol levels during shift cycles among professional firefighters in Korea, this study aims to evaluate the difference between individuals’ stress response and the recovery of their circadian rhythm after working night shifts. (2) Methods: A total of 325 shift firefighters, who were working in 3, 6, 9, or 21 day cycles, participated in the study. Their urinary and serum cortisol levels were measured during the day (09–18), during the night (18–09), and every 24 h (09–09) per shift cycle, and adjustments were made for confounding factors. (3) Results: Serum cortisol levels were significantly increased after working during the night or for 24 h compared with that of working throughout the day. However, whether working night or 24 h shifts, the serum cortisol levels were undoubtedly different based on the 3, 6, 9, or 21 day cycles. In all shift cycles, the urinary cortisol level decreased during the night or throughout the 24 h shifts compared with sleeping during this time, but this was considered to be significantly applicable only to those working in 21 day cycles. Additionally, in serial measurements, the recovery of urinary cortisol secretion after a night or 24 h shift was successful for individuals working in 9 day cycles, but the recovery was delayed for those working in 6 or 21 day cycles. (4) Conclusions: After analyzing the urine cortisol levels, the study indicates that only subjects working in 9 day cycles fully recovered their circadian rhythm while those working in 6 day or 21 day cycles did not completely recover. Therefore, it is important to recognize how stressful night shifts can be, and it is crucial to enhance firefighters’ current shift cycles in order to allow sufficient recovery of their circadian rhythm as well as the prevention of disrupting their circadian rhythm after working at night. Further research is necessary to take into account the amount of work load, the challenges of being sleep deprived, and the individual’s capacity to overcome sleepiness.


Author(s):  
Katherine Q. Philla ◽  
Steve B. Min ◽  
Jody N. Hefner ◽  
Robin S. Howard ◽  
Brian J. Reinhardt ◽  
...  

AbstractThe purpose of this study was to examine the effect of chronic swallowed glucocorticoids on adrenal function during the treatment of eosinophilic esophagitis (EoE) in children.Serum cortisol levels were obtained in children with EoE pre- and post-treatment with swallowed glucocorticoids. Exclusion criteria included those on any additional steroid therapy. Once diagnosed with EoE by esophageal biopsy, subjects were treated based on current standard of care with either swallowed fluticasone or budesonide. At the time of follow-up, esophagogastroduodenoscopy and blood sampling was repeated. Both pre- and post-treatment serum cortisol samples were collected fasting, between 07:00 and 10:00, and determined using a competitive binding method assay. The distribution of differences in cortisol levels between the pre- and post-treatment samples satisfied the assumption for normality and were subsequently analyzed using the paired t-test.Pre- and post-treatment serum cortisol levels were examined in 14 children who met clinical and histological diagnostic criteria for EoE. Mean age was 10.1 years (range 2–17 years) with 71% male and 29% female subjects. Swallowed glucocorticoid treatment included fluticasone in 79% and budesonide in 21% of subjects. Mean dosage of fluticasone was 704 μg daily (range 220–880 μg daily) and budesonide 0.8 mg daily (range 0.5–1 mg daily), along with a mean treatment length of 17 weeks (range 8–43 weeks). No significant difference in serum cortisol was found following treatment with swallowed fluticasone or budesonide (mean change 1.9 μg/dL, p=0.75, SD of the change=21.2).Swallowed glucocorticoid therapy does not appear to significantly affect the adrenal axis in children, and therefore, may represent a safe therapy for EoE.


Author(s):  
Tangeda Padmaja Rao

AbstractIntroductionAdrenal insufficiency has a great impact on the prognosis of patients with traumatic brain injury. In healthy persons during normal day-to-day activity, the concentration of plasma cortisol is high in the morning, decreases during the day and rises again during night. But this diurnal rhythm is abolished in long-term unconscious patients and in those with disturbed sleep cycles. In addition, patients with central nervous system disease, who are conscious but have lesions in the temporal lobe, and the pretectal or hypothalamus area, demonstrate abnormal rhythms.MethodsThis cross-sectional study recruited 33 consecutive patients attending emergency medical departments of Prathima Institute of Medical Sciences Hospital between July 2017 and April 2018 with mild to severe traumatic head injury within 6 h of injury. The selected patients were mainly divided into three groups depending on the Glasgow Coma Scale (GCS) [mild head injury (14–15); moderate head injury (9–13); severe head injury (3–8)]. In each group, 11 patients were selected. GCS was calculated at the time of admission. The adrenal function of the patients was assessed by using the serum cortisol tests.ResultsIn this comparative study of acute head injury among three groups, males are more prone to injury than females, with 81%, 90% and 72% in mild, moderate and severe injuries, respectively. The result mainly shows that the mean cortisol levels estimated were significantly increased in mild head injury and were with greater increase in cases of moderate & severe head injuries. Statistically significant positive correlation was observed between serum cortisol & GCS levels.ConclusionsIn this study of serum cortisol levels in head injury patients, we observed that there is increase in the serum cortisol level immediately after trauma. The increase is linearly related with the severity of head injury. Hence performing serum cortisol test is recommended for the assessment of adrenal function in patients with traumatic head injury.


Author(s):  
K. Rajamanickam ◽  
M. Sameer Ali ◽  
V. Leela

Background: The effect of systemic cortisol on pregnancy rate during early pregnancy in repeat breeding cows was estimated.Methods: Oestrus synchronisation was done in 20 repeat breeders and samples were collected on different days of post-insemination to estimate cortisol.Result: Trans-rectal ultrasonography on 26th day of post insemination revealed a pregnancy rate of 45%. When two groups were compared, serum, salivary and urinary cortisol level of non-pregnant animals were significantly (P less than 0.05) increased than that of pregnant animals on different days of post-insemination. Within non-pregnant animals, serum, salivary and urinary cortisol levels showed a significant (P less than 0.05) variation between different days of post insemination, but this variation was not observed in pregnant animals. Spearman rho correlation revealed positive association (P less than 0.05) of systemic cortisol with pregnancy rate. In non-pregnant animals, salivary and urinary cortisol levels were observed to be positively correlated (P less than 0.05) with serum cortisol. The results indicate that systemic cortisol has influence on pregnancy rate in repeat breeding cows, this may be due to its effect on embryo implantation and hormonal balance, which requires further validation. Association of salivary and urinary cortisol with serum cortisol indicates their use as non-invasive samples to monitor the hypothalamic-pituitary-adrenal axis activity in repeat breeders.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6620 ◽  
Author(s):  
Lisa M. Gunter ◽  
Erica N. Feuerbacher ◽  
Rachel J. Gilchrist ◽  
Clive D.L. Wynne

One of the greatest stressors for dogs living in animal shelters is social isolation. Many studies have demonstrated that human interaction reduces cortisol in shelter dogs, with the possibility that longer periods of interaction may yield greater effects. These types of interventions are contingent upon removing the dog from the kennel and any such reductions in cortisol are often lost when the dog returns to the kennel. More recently, animal shelters are utilizing short-term fostering programs to provide relief from the perceived stresses of kennel life; however the effects of these programs are not well understood. This study assessed the impacts of one- and two-night fostering programs on the urinary cortisol levels, resting pulse rates, longest bout of uninterrupted rest, and proportion of time spent resting of dogs awaiting adoption. Five animal shelters, open and limited-admission facilities, from across the United States participated in the study. During the study, dogs’ urine was collected in the morning before, during, and after fostering stays for cortisol: creatinine analysis. Non-invasive health monitors were worn by the dogs, which collected heart rates and activity levels, in the shelter and in foster homes. In total, 207 dogs participated in the study, and 1,076 cortisol values were used in our analysis. Across all shelters, we found that dogs’ cortisol: creatinine ratios dropped significantly during their fostering stay, but returned to baseline levels after return to the shelter. However, the observed reduction in cortisol varied in magnitude across shelters. We found that dogs of greater weight, age, and average resting pulse rate had higher cortisol levels; and dogs with longer bouts of uninterrupted rest had lower cortisol levels. Dogs had their longest bouts of rest during sleepovers, followed by in the shelter after their sleepovers. Lastly, significant differences were found when comparing in-shelter cortisol values at our five shelters, differences that were in some cases greater than the impact of the fostering intervention itself. Considering the diversity of facilities that participated in this study, it is possible that as yet unstudied, shelter-specific, environmental factors could be contributing to the overall welfare of shelter dogs. Thus while a reprieve from the shelter is impactful for dogs awaiting adoption, mitigating the stressors present in kenneling conditions should also be addressed to improve the lives of shelter dogs.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
C. M. Toledo-Corral ◽  
T. L. Alderete ◽  
M. M. Herting ◽  
R. Habre ◽  
A. K. Peterson ◽  
...  

Abstract Background Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels. Methods In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. Results Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1–7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4–10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4–10 month exposure period associated with lower morning serum cortisol (p < 0.05). Conclusions Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.


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