scholarly journals Impact of Age on Cortisol Secretory Dynamics Basally and as Driven by Nutrient-Withdrawal Stress*

2000 ◽  
Vol 85 (6) ◽  
pp. 2203-2214 ◽  
Author(s):  
M. Bergendahl ◽  
A. Iranmanesh ◽  
T. Mulligan ◽  
J. D. Veldhuis

The present study tests the clinical hypothesis that aging impairs homeostatic adaptations of cortisol secretion to stress. To this end, we implemented a short-term 3.5-day fast as an ethically acceptable metabolic stressor in eight young (ages 18–35 yr) and eight older (ages 60–72 yr) healthy men. Volunteers were studied in randomly ordered fed vs. fasting sessions. To capture the more complex dynamics of cortisol’s feedback control, blood was sampled every 10 min for 24 h for later RIA of serum cortisol concentrations and quantitation of the pulsatile, entropic, and 24-h rhythmic modes of cortisol release using deconvolution analysis, the approximate entropy statistic, and cosine regression, respectively. The stress of fasting elevated the mean (24-h) serum cortisol concentration equivalently in the two age cohorts [i.e. from 7.2± 0.35 to 11.6 ± 0.71 μg/dL in young men and from 7.7 ± 0.39 to 12.6 ± 0.59 μg/dL in older individuals (P < 10−7)]. The rise in integrated cortisol output was driven mechanistically by selective augmentation of cortisol secretory burst mass (P = 0.002). The resultant daily (pulsatile) cortisol secretion rate increased significantly but equally in young (from 94 ± 6.3 to 151 ± 15 μg/dL·day) and older (from 85 ± 5.4 to 145 ± 7.3μ g/dL·day) volunteers (P < 10−4). Nutrient restriction also prompted a marked reduction in the quantifiable regularity of (univariate) cortisol release patterns in both cohorts (P < 10−4). However, older men showed loss of joint synchrony of cortisol and LH secretion even in the fed state, which failed to change with metabolic stress (P < 10−6). In addition, older individuals maintained a premature (early-day) cortisol elevation in the fed state and unexpectedly evolved an anomalous further cortisol phase advance of 99 ± 16 min during fasting (P < 10−5). Caloric deprivation in aging men also disproportionately elevated the mesor of 24-h rhythmic cortisol release (P = 10−7) and elicited a greater increment in the mean day-night variation in cortisol secretory-burst mass (P < 0.01 vs. young controls). Lastly, short-term caloric depletion in older subjects paradoxically normalized their age-associated suppression of the 24-h rhythm in cortisol interburst intervals. In summary, acute metabolic stress in healthy aging men (compared with young individuals) unmasks distinct, albeit complex, disruption of cortisol homeostasis. These dynamic anomalies impact the feedback-dependent and time-sensitive coupling of pulsatile and 24-h rhythmic cortisol secretion. Nutrient-withdrawal stress in the older male heightens the cortisol phase disparity already evident in fed elderly individuals. Conversely, the stress of fasting in young men paradoxically reproduces selected features of the aging unstressed (fed) cortisol axis; viz., abrogation of joint cortisol-LH synchrony and suppression of the normal diurnal variation in cortisol burst frequency. Whether fasting would unveil analogous disruption of feedback-dependent control of the corticotropic axis in healthy aging women is not yet known.

2000 ◽  
Vol 85 (11) ◽  
pp. 4028-4035
Author(s):  
M. Bergendahl ◽  
A. Iranmanesh ◽  
C. Pastor ◽  
W. S. Evans ◽  
J. D. Veldhuis

Short-term fasting as a metabolic stress evokes prominent homeostatic reactions of the reproductive, corticotropic, thyrotropic, somatotropic, and leptinergic axes in men and women. Although reproductive adaptations to fasting are incompletely studied in the female, nutrient deprivation can have major neuroendocrine consequences in the follicular phase. Unexpectedly, a recent clinical study revealed relatively preserved sex steroid and gonadotropin secretion during short-term caloric restriction in the midluteal phase of the menstrual cycle. This observation suggested that female stress-adaptive responses might be muted in this sex steroid-replete milieu. To test this hypothesis, we investigated the impact of fasting on daily cortisol secretion in healthy young women during the midluteal phase of the normal menstrual cycle. Eight volunteers were each studied twice in separate and randomly ordered short-term (2.5-day) fasting and fed sessions. Pulsatile cortisol secretion, 24-h rhythmic cortisol release, and the orderliness of cortisol secretory patterns were quantified. Within-subject statistical comparisons revealed that fasting increased the mean serum cortisol concentration significantly from a baseline value of 8.0 ± 0.61 to 12.8 ± 0.85 μg/dL (P = 0.0003). (For Systeme International conversion to nanomoles per L, multiply micrograms per dL value by 28.) Pulsatile cortisol secretion rose commensurately, viz. from 101 ± 11 to 173 ± 16 μg/dL/day (P = 0.0025). Augmented 24-h cortisol production was due to amplification of cortisol secretory burst mass from 8.2 ± 1.5 to 12.9 ± 2.0μ g/dL (P = 0.017). In contrast, the estimated half-life of endogenous cortisol (104 ± 9 min), the calculated duration of underlying cortisol secretory bursts (16 ± 7 min) and their mean frequency (14 ± 2/day) were not altered by short-term fasting. The quantifiable orderliness of cortisol secretory patterns was also not influenced by caloric restriction. Nutrient deprivation elevated the mean of the 24-h serum cortisol concentration rhythm from 12.4 ± 1.3 to 18.4 ± 1.9 μg/dL (P = 0.0005), without affecting its diurnal amplitude or timing. Correlation analysis disclosed that fasting reversed the positive relationship between cortisol and LH release evident in the fed state, and abolished the negative association between cortisol and GH as well as between cortisol and leptin observed during nutrient repletion (P < 0.001). Pattern synchrony between cortisol and GH as well as that between cortisol and LH release was also significantly disrupted by fasting stress. In summary, short-term caloric deprivation enhances daily cortisol secretion by 1.7-fold in healthy midluteal phase young women by selectively amplifying cortisol secretory burst mass and elevating the 24-h rhythmic cortisol mean. Augmentation of daily cortisol production occurs without any concomitant changes in cortisol pulse frequency or half-life or any disruption of the timing of the 24-h rhythmicity or orderliness of cortisol release. Fasting degrades the physiological coupling between cortisol and LH, cortisol and GH, and cortisol and leptin secretion otherwise evident in calorie-sufficient women. We conclude that the corticotropic axis in the young adult female is not resistant to the stress-activating effects of short-term nutrient deprivation, but, rather, evinces strong adaptive homeostasis both monohormonally (cortisol) and bihormonally (cortisol paired with GH, LH, and leptin).


1984 ◽  
Vol 105 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Jean-Noel Hugues ◽  
Albert G. Burger ◽  
A. Eugene Pekary ◽  
Jerome M. Hershman

Abstract. Nutrition influences thyroid function at the level of TSH secretion, at the level of monodeiodination, and possibly elsewhere. In order to study the effect of starvation on TSH secretion, 8 healthy male volunteers fasted for 30 h and were then refed with 800 kcal. Refeeding was performed at 19.00 h and blood was sampled at 20 min intervals until midnight. Control experiments were performed in the same subjects both when they were normally fed and when the starvation period was prolonged a further 5 h until midnight. Starvation decreased serum TSH levels to below 1 mU/l, and without refeeding the nocturnal peak of the TSH nycthemeral rhythm was abolished. With refeeding serum TSH tended to increase towards midnight and was significantly higher than during starvation. However, the serum TSH levels remained significantly below those at the same time of the day in the absence of a preceding starvation period. Serum T3 levels were significantly lower than in the fed state. The mean values were 1.84 ± 0.03 vs 2.30 ± 0.06 nmol/l (120 ±2 vs 150 ± 4 ng/100 ml, mean ± sem P < 0.01). Refeeding did not result in a measurable change in serum T3 concentration (1.80 ± 0.05 nmol/l; 120 ± 3 ng/100 ml, mean ± sem, n.s.). The contrary was true for rT3 levels which increased in starvation and tended to fall with refeeding, but this decrease was not significant. As glucocorticoids have been implicated in the control of monodeiodination and TSH secretion, serum cortisol levels were also measured. They did not differ during the 3 experimental periods. The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion. The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion.


1993 ◽  
Vol 128 (6) ◽  
pp. 521-528 ◽  
Author(s):  
Ali Iranmanesh ◽  
German Lizarralde ◽  
Johannes D Veldhuis

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), β-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77±15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma β-endorphin concentration, the maximal value of which was 96±11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734±14 nmol/l. Maximal plasma ACTH and β-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5±2.7 and 10.6±2.0 pmol·I−1·min−1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114±20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 μg (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4±0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088±137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, β-endorphin and cortisol were 17±0.6, 22±1.7 and 65±5.3 min, respectively. In summary, deconvolution analysis revealed a rapid coordinate activation of ACTH, β-endorphin and cortisol secretion after hypoglycemic stress, which correlated closely but temporally preceded increases in the respective plasma concentrations. Our inference that only a small fraction of pituitary ACTH content is released during hypoglycemic stress emphasizes the large reserve capability of the pituitary corticotropes. The percentage response of adrenal gland to the metabolic stress of hypoglycemia was of lesser magnitude, possibly owing to the rate-limiting properties of cortisol biosynthesis. We conclude that kinetic responses of the hypothalamic—pituitary—adrenal axis to hypoglycemic stress exhibit exquisite temporal synchrony and manifest a marked reserve capacity.


2005 ◽  
Vol 288 (4) ◽  
pp. E775-E781 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Nathan J. D. Veldhuis ◽  
Daniel M. Keenan ◽  
Ali Iranmanesh

Testosterone (Te) concentrations fall gradually in healthy aging men. Postulated mechanisms include relative failure of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and/or gonadal Te secretion. Available methods to test Leydig cell Te production include pharmacological stimulation with human chorionic gonadotropin (hCG). We reasoned that physiological lutropic signaling could be mimicked by pulsatile infusion of recombinant human (rh) LH during acute suppression of LH secretion. To this end, we studied eight young (ages 19–30 yr) and seven older (ages 61–73 yr) men in an experimental paradigm comprising 1) inhibition of overnight LH secretion with a potent selective GnRH-receptor antagonist (ganirelix, 2 mg sc), 2) intravenous infusion of consecutive pulses of rh LH (50 IU every 2 h), and 3) chemiluminometric assay of LH and Te concentrations sampled every 10 min for 26 h. Statistical analyses revealed that 1) ganirelix suppressed LH and Te equally (> 75% median inhibition) in young and older men, 2) infused LH pulse profiles did not differ by age, and 3) successive intravenous pulses of rh LH increased concentrations of free Te (ng/dl) to 4.6 ± 0.38 (young) and 2.1 ± 0.14 (older; P < 0.001) and bioavailable Te (ng/dl) to 337 ± 20 (young) and 209 ± 16 (older; P = 0.002). Thus controlled pulsatile rh LH drive that emulates physiological LH pulses unmasks significant impairment of short-term Leydig cell steroidogenesis in aging men. Whether more prolonged pulsatile LH stimulation would normalize this inferred defect is unknown.


1984 ◽  
Vol 13 (4) ◽  
pp. 261-266 ◽  
Author(s):  
Harvey A. Sternbach ◽  
Irl Extein ◽  
Donald R. Sweeney ◽  
Mark S. Gold ◽  
A. L. C. Pottash

The authors examined the relationship between both pre-dexamethasone 8:00 AM serum cortisol level and the dexamethasone suppression test (DST) with urinary 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion in a group of fifteen men and fourteen women with unipolar depression. No significant difference was found between the mean MHPG excretion for either male or female DST suppressors or non-suppressors. No significant correlation was found between the pre-dexamethasone 8:00 AM serum cortisol level and urinary MHPG. These results do not support the hypothesis that DST non-suppression in depression is related to central noradrenergic deficiency.


1997 ◽  
Vol 136 (4) ◽  
pp. 394-400 ◽  
Author(s):  
Gerrit van den Berg ◽  
Steven M Pincus ◽  
Johannes D Veldhuis ◽  
Marijke Frölich ◽  
Ferdinand Roelfsema

Abstract We investigated the episodicity of 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 25 healthy matched controls, with a recently introduced scale- and modelindependent regularity statistic, approximate entropy (ApEn). The mean (± s.e.m.) ApEn value for plasma ACTH concentrations in Cushing's disease was 1·3817 ± 0·033, and in controls 0·8394 ± 0·049 (P< 10−10); for plasma cortisol concentrations the values were 1·4575 ± 0·052 and 0·8637 ± 0·020 respectively (P<10−10), implying greater irregularity of release for both hormones in Cushing's subjects. The calculated sensitivity and specificity of ApEn for ACTH profiles were 94% and 100% respectively. For cortisol the sensitivity and specificity were both 100%. ApEn was not correlated with sex, age, or the total 24-h secretion rate of ACTH and cortisol in patients and controls. The increased ApEn in patients with Cushing's disease points to an increased disorderliness of ACTH and cortisol secretion compared with healthy controls. In conjunction with the available literature, we hypothesize more generally that autonomous endocrine tumors may be typified by reduced regularity, orderliness, or synchrony of the time structure of hormone release. European Journal of Endocrinology 136 394–400


VASA ◽  
2019 ◽  
Vol 48 (5) ◽  
pp. 413-417 ◽  
Author(s):  
Serge Couzan ◽  
Jean-François Pouget ◽  
Claire Le Hello ◽  
Céline Chapelle ◽  
Silvy Laporte ◽  
...  

Summary. Background: Theoretically progressive compression stockings, which produce a higher compression at the calf than at the ankle level, improve venous return flow without exacerbating peripheral arterial insufficiency (PAD). We aimed to evaluate the short-term tolerance of elastic progressive compression stockings on peripheral arterial vascularisation in patients with symptomatic PAD and associated mild venous insufficiency. Patients and methods: Monocentric, prospective, open pilot study of 18 patients (acceptability study, 6 x 6 plan) evaluating the short-term tolerance of progressive compression stockings (18 ± 2 mmHg at calf and 8 ± 2 mmHg at ankle level) in patients with PAD (ankle brachial index ABI > 0.60 < 0.75) and chronic venous insufficiency (C1s–C4 stages of the CEAP classification). Day 15 tolerance was evaluated by a composite primary criteria comprising: no decrease > 15 % of ABI on each side, no decrease > 15 % of toe brachial index (TBI) on each side and no decrease > 25 % of the number of active plantar flexions performed while standing. Results: The proportion of men was 77.8 %, mean age was 77.3 ± 7.5 years and no patient were diabetic. At inclusion, the mean low ABI was 0.60 ± 0.04 and the mean high ABI was 0.77 ± 0.18. The mean low TBI was 0.32 ± 0.09 and the mean high TBI 0.46 ± 0.15. The mean number of active standing plantar flexions was 33.0 ± 5.0. The majority of the patients were classified in CEAP C2s and C3 classes (class 2: 16.7 %, class C2s: 27.8 %, class C3: 44.4 %, class C4: 5.6 % and class C4s: 5.6 %). Poor tolerance occurred in no patient. By day 30, no patient had worsening of their arterial and venous symptoms. No adverse events occurred during the study. Conclusions: These results suggest a high tolerance of progressive elastic stockings (18 ± 2 mmHg at calf and 8 ± 2 mmHg at ankle level) in symptomatic PAD.


Author(s):  
Shivananda B Nayak ◽  
Dharindra Sawh ◽  
Brandon Scott ◽  
Vestra Sears ◽  
Kareshma Seebalack ◽  
...  

Purpose: i) To determine the relationship between the cardiac biomarkers ST2 and NT-proBNP with ejection fraction (EF) in heart failure (HF) patients. ii) Assess whether a superiority existed between the aforementioned cardiac markers in diagnosing the HF with reduced EF. iii) Determine the efficacy of both biomarkers in predicting a 30-day cardiovascular event and rehospitalization in patients with HF with reduced EF iv) To assess the influence of age, gender, BMI, anaemia and renal failure on the ST2 and NT-proBNP levels. Design and Methods: A prospective double-blind study was conducted to obtain data from a sample of 64 cardiology patients. A blood sample was collected to test for ST2 and NT-proBNP. An echocardiogram (to obtain EF value), electrocardiogram and questionnaire were also obtained. Results: Of the 64 patients enrolled, 59.4% of the population had an EF less than 40%. At the end of the 30- day period, 7 patients were warded, 37 were not warded, one died and 17 were non respondent. Both biomarkers were efficacious at diagnosing HF with a reduced EF. However, neither of them were efficacious in predicting 30-day rehospitalization. The mean NT-proBNP values being: not rehospitalized (2114.7486) and 30 day rehospitalization (1008.42860) and the mean ST2 values being: not rehospitalized (336.1975), and 30-day rehospitalization. (281.9657). Conclusion: Neither ST2 or NT-proBNP was efficacious in predicting the short- term prognosis in HF with reduced EF. Both however were successful at confirming the diagnosis of HF in HF patients with reduced EF.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esteban Balseiro ◽  
Cecilia Laspoumaderes ◽  
Facundo Smufer ◽  
Laura Wolinski ◽  
Beatriz Modenutti

AbstractIn this study, we analysed how short term temperature fluctuation interacts with nutrient limitation in the vertical migrating Daphnia commutata. We hypothesize that short term (daily) temperature fluctuation will alleviate nutrient limitation. We carried out experiments analysing growth rates, phosphorus and RNA content of D. commutate grown under four different temperature regimes and two P-limited conditions. Our experiments showed that individuals grown under fluctuating temperature grew more than at the mean temperature. We estimated the expected sizes for the 15 °C treatment based on the Q10 and for the fluctuating temperature treatment. These expected sizes for both treatments resulted well below the observed ones. The P and RNA content of individuals grown at 10 °C were significantly higher than those at 20 °C, and when individuals grown at 10 °C were translocated to 20 °C they exerted an increased growth rate. Our results suggest that, under a regime of diel vertical migration, the temperature alternation would allow migrating organisms to alleviate the effect of severe nutrient limitation maintaining population growth. Under a scenario of global warming, where epilimnetic temperatures will increase, lake temperature will interact with nutrient limitation for consumers, but, organisms may be able to face these changes if they can still regularly move from a cold hypolimnion to a warmer epilimnion.


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