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At least 109 records · Page 6Linked to original sources
PubMed1993

Reproducibility of the cortisol response to stimulation with a low dose of ACTH(1-24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics.

We compared the reproducibility and repeatability of the acute adrenal response to low doses (90 and 500 ng/1.73 m2) of Synacthen (ACTH(1-24)) with that of the standard dose (250 micrograms/1.73 m2). We also examined the effect of basal cortisol levels on peak values achieved after stimulation with a low dose. ACTH(1-24) was given to six male volunteers: 90 ng/1.73 m2 twice at 90-min intervals on day 1, and 90 and 500 ng/1.73 m2 once on day 2 and 250 micrograms/1.73 m2 once on day 3. The rise in serum cortisol concentration with repeated low doses of ACTH was not attenuated (161 +/- 49 (S.D.) nmol/l on initial vs 150 +/- 41 nmol/l on repeat stimulation; P = 0.5) and this was reproducible (161 +/- 49 nmol/l on day 1 vs 148 +/- 15 nmol/l on day 2; P = 0.6). A dose of 500 ng ACTH(1-24)/1.73 m2 produced a maximal adrenal response in that the rise in serum cortisol concentration at 20 min was identical with that produced at the same time by the standard dose of 250 micrograms/1.73 m2. There was a strong positive correlation between the basal cortisol level and peak cortisol concentration after low-dose ACTH stimulation (r = 0.93, P < 0.001) but not between the basal cortisol level and the incremental rise (r = -0.1, P = 0.69). These results suggest that the cortisol response to low-dose ACTH stimulation is reproducible and not attenuated by repeat stimulation at 90-min intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed2002

Influence of sex and gonadal status of sheep on cortisol secretion in response to ACTH and on cortisol and LH secretion in response to stress: importance of different stressors.

There are sex differences in the response to stress and in the influence of stress on reproduction which may be due to gonadal steroids but the nature of these differences and the role of the gonads are not understood. We tested the hypotheses that sex and the presence/absence of gonads (gonadal status) will influence the cortisol response to injection of ACTH, insulin-induced hypoglycaemia and isolation/restraint stress, and that sex and gonadal status will influence the secretion of LH in response to isolation/restraint stress. Four groups of sheep were used in each of three experiments: gonad-intact rams, gonadectomised rams, gonad-intact ewes in the mid-luteal phase of the oestrous cycle and gonadectomised ewes. In Experiment 1 (n=4/group), jugular blood samples were collected every 10 min for 6 h; after 3 h, two animals in each group were injected (i.v.) with ACTH and the remaining two animals were injected (i.v.) with saline. Treatments were reversed 5 days later so that every animal received both treatments. Experiment 2 (n=4/group) used a similar schedule except that insulin was injected (i.v.) instead of ACTH. In Experiment 3 (n=5/group), blood samples were collected every 10 min for 16 h on a control day and again 2 weeks later when, after 8 h of sampling, all sheep were isolated and restrained for 8 h. Plasma cortisol was significantly (P<0.05) elevated following injection of ACTH or insulin and during isolation/restraint stress. There were no significant differences between the sexes in the cortisol response to ACTH. Rams had a greater (P<0.05) cortisol response to insulin-induced hypoglycaemia than ewes while ewes had a greater (P<0.05) cortisol response to isolation/restraint stress than rams. There was no effect of gonadal status on these parameters. Plasma LH was suppressed (P<0.05) in gonadectomised animals during isolation/restraint stress but was not affected in gonad-intact animals, and there were no differences between the sexes. Our results show that the sex that has the greater cortisol response to a stressor depends on the stressor imposed and that these sex differences are likely to be at the level of the hypothalamo-pituitary unit rather than at the adrenal gland. Since there was a sex difference in the cortisol response to isolation/restraint, the lack of a sex difference in the response of LH to this stress suggests that glucocorticoids are unlikely to be a major mediator of the stress-induced suppression of LH secretion.

Adrenocorticotropic Hormone↗
PubMed1980

Dextroamphetamine and cortisol in depression. Morning plasma cortisol levels suppressed.

Dextroamphetamine sulfate administered intravenously in the morning to 11 unmedicated depressed patients suppressed previously elevated plasma cortisol levels to normal in 90 minutes, a fall of 33% from baseline. Ten other depressed patients, without amphetamine, maintained high cortisol levels during the same time period. In each of five normal young men, amphetamine identically administered stimulated a rise in cortisol between 15 and 30 minutes after infusion, an acute response absent in ten of the 11 depressed patients; by 90 minutes after amphetamine administration, plasma cortisol had fallen to normal and identical levels in both groups. Since noradrenalin normally inhibits hypothalamic corticotropin releasing factor (and adrenocorticotropic hormone) secretion, a noradrenergic deficit may account for cortisol hypersecretion in depression; amphetamine may transiently "correct" this deficit in depressed patients, thereby reducing their cortisol secretion.

Adult↗
PubMed1987

Determination of the urinary cortisol production rate using (1,2,3,4-13C)cortisol. Isotope dilution analyses at very small enrichments.

An isotope dilution mass spectrometric method to determine the urinary cortisol production rate (CPR) in babies and children is described. The method uses stable isotopically labelled (1,2,3,4-13C)cortisol. The tracer is intravenously administered to the patient and urine is collected for the following three days. Following extraction, enzymic hydrolysis, purification and isolation by high-performance liquid chromatography (HPLC) the urinary cortisol metabolites tetrahydrocortisone, tetrahydrocortisol, alpha- and beta-cortolone are separately oxidized the common product, 11-oxo-aetiocholanolone. The methyl oxime tert-butyldimethylsilyl ether derivative (MO TBDMS) was analysed by gas chromatography mass spectrometry. Quantification of the isotope enrichment was carried out by unlabelled, and at m/z 348 for labelled 11-oxo-aetiocholanolone. HPLC isolation of the metabolites together with the oxidation step allowed very small isotope enrichments, sometimes down to 0.1% (1:1000), to be reliably measured against a linear calibration graph containing 0 to 1% (13C4) enrichments. The standards for the calibration graph were synthesized from mixtures of labelled (13C4) cortisol and natural cortisol, and the calibration graph was prepared each time samples were measured. The long term instrumental precision of the isotope dilution analyses was 0.91% for a derivatized sample containing a (13C4) enrichment of 0.5% (measured on six different days over seven months). The coefficient of variation of the complete procedure for the four cortisol metabolites was between 1.17 and 2.14%. The clinical applicability of the method is demonstrated by presenting the results of a CPR determination in a patient.

Adolescent↗
PubMed1986

Cortisol succinate is slowly hydrolysed in organ cultures of porcine articular tissues and is not equivalent to cortisol.

The pro-drug cortisol succinate is frequently used as a substitute for cortisol in organ cultures. We found, however, that in Dulbecco's modified Eagle's medium the time taken for the ester to undergo 50 per cent hydrolysis (t1/2) to cortisol was 75 h. When 15 per cent heat-inactivated normal rabbit serum was present t1/2 decreased to 47 h, but the rate of hydrolysis was not further increased in the presence of porcine articular cartilage or minced synovial tissue. When frozen and thawed synovium was present t1/2 decreased to 33 h, presumably due to the release of carboxyl-esterases from the disrupted cells. The level of tetrahydrocortisol was low in all of the cultures. The slow hydrolysis of cortisol succinate resulted in the exposure of the tissues to undesirable fluctuations in the concentration of active hormone, which decreased to low levels at each medium change. Thus, in co-cultures of porcine synovium and articular cartilage, cortisol had a greater inhibitory effect than cortisol succinate on the breakdown of cartilage matrix caused by synovial tissue.

Animals↗
PubMed1995

Total cortisol, free cortisol, and growth hormone associated with brief social separation experiences in young macaques.

Many behavioral, immunological, and physiological consequences or brief maternal separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina) have been documented. However, the impact of social separation on plasma cortisol and growth hormone is unknown for these particular species. In the present study, the behavioral and endocrinological consequences of a 2-week maternal separation in socially housed infant bonnet and pigtail monkeys were followed. In seven pairs (separated and matched control) of bonnet and six pairs of pigtail infants, plasma was obtained under baseline, separated, and reunion conditions twice weekly for the duration of the study. Blood samples were obtained from both infants of the pair in approximately 10 min. Plasma total cortisol, free cortisol, and growth hormone were measured in these samples. Focal animal behavioral observations were made on all subjects twice daily throughout the study period. In both species, total cortisol and free cortisol rose immediately following maternal separation in comparison to the matched nonseparated controls and returned to basal levels (e.g., that of matched nonseparated controls) following reunion with the mother. In contrast, plasma growth hormone rose only in the pigtail infants over a time course that peaked around the time of reunion. Multiple regression techniques indicated for the first week of separation, in the separated but not control subjects, that mean plasma free and total cortisol was positively related to distress behaviors (vocalization and postural slouch) observed during this week and negatively related to social behaviors (play and proximity to others) noted during the same period. In contrast, plasma growth hormone was related to both species and sex of the subjects but unrelated to behavioral variables.

Animals↗
PubMed1998

Native urotensins influence cortisol secretion and plasma cortisol concentration in the euryhaline flounder, platichthys flesus.

Adrenocorticotrophic hormone (ACTH) and flounder urotensins I and II (UI and UII) stimulate cortisol secretion of isolated interrenal/head kidney preparations of seawater (SW)-adapted flounder. UI and UII at concentrations of 10(-6) and 10(-7) M, respectively, increased cortisol secretion when acting on SW-derived interrenal but did not affect cortisol secretion in tissue derived from freshwater (FW) fish. Combined UI and UII had no synergistic or additive steroidogenic action, but either 10(-7) M UI or 10(-7) M UII in combination with ACTH produced a very marked, additive, or synergistic steroidogenic response, most apparent on interrenal derived from FW fish. These results suggest that urotensins enhance the steroidogenic action of ACTH in flounder. In all cases, significant steroidogenesis was apparent within 1 h postperifusion of ligands. In SW-adapted flounder intraarterial infusion of UII in vivo caused a concentration-dependent increase in plasma cortisol concentration within 1 h after infusion, while after 5 x 10(-6) M UI infusion a similar trend was evident but this did not achieve statistical significance. The data suggest that the caudal neurosecretory system may control interrenal cortisol secretion, to modulate cortisol secretion independently of the hypophysial axis, perhaps in response to specific stress-induced or osmoregulatory challenge.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Progressively elevated levels of biologically active (free) cortisol during pregnancy by a direct radioimmunological assay of diffusible cortisol in an equilibrium dialysis system.

The measurement of free cortisol would be preferable with respect to the total hormone content, since it yields more reliable information about the plasma levels of the biologically active cortisol. We have developed a new method for the determination of the apparent free plasma cortisol concentration (AFCC) by means of direct radioimmunological measurement of dialyzed cortisol. The AFCC was measured in 23 plasma pools obtained from normal pregnant women at various gestational times and in 18 nonpregnant women. The mean AFCC was 19.5 +/- 7.1 ng/ml in pregnant women and 9.0 +/- 6.2 ng/ml in nonpregnant women (p less than 0.005). The percent of free cortisol (%FC) showed a progressive increase during pregnancy reaching the lower limits of the normal range at the third trimester. However, the mean of %FC was significantly lower (p less than 0.005) in pregnant women than in nonpregnant women. Our data show a progressive increase of biologically active cortisol during pregnancy.

Dialysis↗
PubMed1991

Measurement of the cortisol production rate in two sisters with 17 alpha-hydroxylase deficiency using [1,2,3,4-13C]cortisol and isotope dilution mass spectrometry.

[1,2,3,4-13C]cortisol was i.v. administered to two sisters aged 11 yr (patient I) and 3 yr (patient II) who suffer from 17 alpha-hydroxylase deficiency. This is the first time that the cortisol production rate (CPR) in patients with 17 alpha-hydroxylase deficiency has been measured with a stable labelled tracer using the urinary method. The urine was collected for 3 days. High-performance liquid chromatography (HPLC) of approximately 100 ml urine extracts was carried out to isolate the small amount of cortisol metabolites excreted. The cortisol metabolites were oxidized to 11-oxo-aetiocholanolone. The isotope dilution in the methyl oxime tert-butyldimethylsilyl ether derivatives was measured by selected ion monitoring gas chromatography/mass spectrometry (GC/MS). The CPR calculated from tetrahydrocortisone (THE) and the cortolones was 765 and 536 nmol/day, respectively in patient I. The CPR in patient II was only calculated from THE and was 62 nmol/day. If radioactive labelled cortisol had been used, much larger quantities of urine would have been needed for isolation of sufficient mass of metabolites, even then purification may have been difficult. Steroid profiling of 1 ml urine samples by GC and identification by GC/MS revealed high concentrations of pregnenolone, progesterone, 11 beta-hydroxy progesterone and corticosterone metabolites. Tetrahydrocorticosterone and 5 alpha-tetrahydrocorticosterone were found in urine at elevated excretions of 2.5 and 5.7, 0.9 and 2.0 mumols/24 h, in patients I and II respectively. No cortisol metabolites were detected by routine GC or GC/MS as the low amounts excreted co-eluted with the relatively abundant corticosterone metabolites.

Adrenal Hyperplasia, Congenital↗
PubMed2000

The use of deuterium-labeled cortisol for in vivo evaluation of renal 11beta-HSD activity in man: urinary excretion of cortisol, cortisone and their A-ring reduced metabolites.

This study describes a new approach using stable isotope methodology in evaluating 11beta-HSD activities in vivo based on urinary excretion of cortisol, cortisone, and their A-ring reduced metabolites. The method involved the measurement of deuterium-labeled cortisol and its deuterium-labeled metabolites by GC/MS simultaneously with endogenous cortisol, cortisone, and their A-ring reduced metabolites after oral administration of deuterium-labeled cortisol to normal human subjects. This stable isotope approach offered unique advantages in assessing the appropriateness of measuring unconjugated and total (unconjugated + conjugated) cortisol, cortisone, and their A-ring reduced metabolites in urine as indices of renal 11beta-HSD2 activity in man. Our results strongly support that the measurement of urinary unconjugated cortisol and cortisone is a significant advance in assessing 11beta-HSD2 activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Synthesis of multi-labeled cortisols and cortisones with (2)H and (13)C for study of cortisol metabolism in humans.

A method is described for the preparation of multi-labeled cortisol and cortisone with (13)C and (2)H via the indan synthon method, starting from chiral 11-oxoindanylpropionic acid. [1, 3-(13)C(2)]Acetone was used for the syntheses of [1,2,4, 19-(13)C(4)]cortisol (cortisol-(13)C(4)) and [1,2,4, 19-(13)C(4)]cortisone (cortisone-(13)C(4)), and [1,3-(13)C(2),1,1,1, 3,3,3-(2)H(6)]acetone was for [1,2,4,19-(13)C(4),1,1,19,19, 19-(2)H(5)]cortisol (cortisol-(13)C(4),(2)H(5)) and [1,2,4, 19-(13)C(4),1,1,19,19,19-(2)H(5)]cortisone (cortisone-(13)C(4), (2)H(5)). The chemical shifts for the (13)C and (1)H NMR spectra of cortisol and cortisone were fully assigned.

Carbon Isotopes↗
PubMedDate not supplied

Effect of chronic stress associated with unemployment on salivary cortisol: overall cortisol levels, diurnal rhythm, and acute stress reactivity.

This study examined the effect of chronic stress associated with unemployment on the magnitude of salivary cortisol excretion, on the diurnal rhythm of cortisol, and on cortisol reactivity to acute naturalistic stressors using Experience Sampling Methodology (ESM). Employed (N = 60) and unemployed (N = 60) subjects were studied for 2 days. Subjects were beeped 6 times per day by a preprogrammed wristwatch to assess acute stressors; 25 minutes after each ESM-beep, subjects were beeped a second time for saliva samples. The groups did not differ in their overall cortisol excretion or in cortisol reactivity to acute daily stressors. Compared to employed subjects, unemployed subjects had a diurnal pattern of cortisol excretion with relatively higher morning and lower evening levels. Subjects' daily activities and their locations were associated with diurnal rhythm differences.

Adult↗
PubMed1995

Circadian rhythm of cortisol confounds cortisol responses to exercise: implications for future research.

To investigate whether measurements of cortisol responses to exercise are confounded by neglect of the hormone's circadian rhythm, we measured the serum and salivary cortisol responses of eight women to 40 min of 70% maximal oxygen consumption treadmill exercise beginning at 0800 and 2000. Responses were calculated relative to the usually employed preexercise concentrations and also to concentrations at the same times of another day while subjects were at rest. Compared with areas under response curves (AUCs) calculated relative to their circadian baselines, AUCs for serum and salivary cortisol calculated by reference to preexercise concentrations were underestimated (serum, P < 0.001; salivary, P < 0.01) by 93 and 84% in the morning and by 37 and 35% in the evening, respectively. Calculated by the usual preexercise baseline method, rises in serum and salivary cortisol were similarly underestimated. More accurately calculated relative to their circadian baselines, serum and salivary cortisol AUCs were similar (P = 0.63 and P = 0.37, respectively) in the morning and evening, as were their rises (P = 0.23 and P = 0.70, respectively). In future investigations of the existence and magnitude of cortisol responses, those responses must be calculated relative to the hormone's circadian baseline.

Adolescent↗