Resting Plasma Cortisol Concentrations Research Articles

Evidence for Ototopical Glucocorticoid-Induced Decrease in Hypothalamic-Pituitary-Adrenal Axis Response and Liver Function

To clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis (HPA) activity and altered hepatic metabolism, one commercially available dexamethasone-containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function. Ten beagle dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 d in a single-blind, placebo-controlled study. Resting cortisol concentrations were assessed before, during, and after treatment using an RIA system. Adrenal function and HPA feedback sensitivity were measured by a standard dose (250 microg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function was studied, and blood cell counts were made. Ototopical dexamethasone treatment induced a marked suppression (to about 100%) of resting plasma cortisol concentrations below the placebo effect (P < 0.0001) within the first 11 d, and these remained reduced during the entire treatment period up to d 19. As well, an ACTH stimulation test found a markedly reduced rise in plasma cortisol concentrations (P = 0.0004). Concomitantly, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. Although cortisol levels and hematological parameters returned to baseline 7 d after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the auditory canal to suppress HPA function as well as to alter metabolic and hemopoietic profiles. Thus, in long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation to stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.

Prenatal Glucocorticoid Modifies Hypothalamo-Pituitary-Adrenal Regulation in Prepubertal Guinea Pigs

We hypothesized that exposure to synthetic glucocorticoid during rapid brain growth (d50–52, birth = 68 days) in fetal guinea pigs modifies hypothalamo-pituitary-adrenal (HPA) function after birth, and that this involves changes in central corticosteroid receptor regulation. On the basis of our previous studies, we proposed that this effect is sex-specific. Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on d50–51 of gestation, and juvenile offspring were euthanized at rest or following isolation stress on postnatal day 18. Dexamethasone increased the length of gestation (1.5 days) and altered body and organ (brain, heart, adrenal) growth. Resting plasma cortisol concentrations were significantly elevated in young male, but not female guinea pigs exposed to dexamethasone as fetuses. In female offspring born to dexamethasone-treated mothers, cortisol responses to isolation stress were attenuated. In males, elevated basal cortisol levels were not increased further by isolation. In the brain, hippocampal glucocorticoid receptor (GR) mRNA levels were significantly lower (10–25%) in females exposed to dexamethasone in utero. In contrast, GR mRNA levels were elevated (10–20%) in males from this prenatal treatment group. Mineralocorticoid receptor mRNA in the limbic system and GR mRNA levels in the pars distalis were unaffected. Pro-opiomelanocortin mRNA was significantly lower (30%) in the male pars intermedia following dexamethasone exposure. In conclusion, prenatal glucocorticoid exposure affects growth and HPA function as well as limbic and hypothalamic GR expression in juvenile offspring, and these effects are highly sex-specific.

The effects of stocking density and social interaction on acute stress response in Nile tilapia Oreochromis niloticus (L.) fingerlings

Several researchers have demonstrated that the stocking density and social interactions between conspecific fish have significant influence on stress response. Nile tilapia Oreochromis niloticus (L.) is a teleost fish with hierarchical organization. Nile tilapia fingerlings (20 ± 5 g) were distributed in 30 tanks, 12 tanks with single fish and six with paired, groups of five and 10 fish, respectively, and held in these 100-L plastic tanks for 60 days. Six tanks of single fish and three of other groups received an acute stressor on the 61st day. The control fish reared singly and in pairs showed a plasma cortisol concentration similar to that normally found as a resting cortisol concentration in other fish. One surprising result was the absence of the formation of a hierarchical dominant/submissive relation between the fish held in pairs. One possible explanation for this result is the volume of the tank, so that each fish exerted a territorial position in a corner of the tank, and the fighting and antagonistic encounters did not occur. In the five- and 10-fish groups, the resting plasma cortisol concentrations were higher, which may indicate a chronic stress response during the 60 days of the experiment, attributable to social stress. The application of an acute stressor significantly increased the plasma cortisol levels in all stocking densities, with values reaching 135–298 ng mL− 1. When comparing the stressed fish, the 10-fish groups showed a more intense stress response in relation to the other groups.

Maturation of cortisol responses to adrenocorticotropic hormone in twin fetal sheep in vivo

Objective: Adrenal steroidogenesis is important for maturation of fetal organ systems and plays a role in triggering parturition in ovine pregnancies. Studies have suggested a differential increase in baseline cortisol between twin gestations near term. Our aim was to further delineate the mechanisms responsible for the differences between the hypothalamic-pituitary-adrenal axes of twin fetuses in vivo. Study Design: Surgery was performed on pregnant ewes (n = 6) with twin gestations to implant fetal vascular catheters. After recovery but while the subjects were resting, plasma cortisol concentrations were similar in both fetuses. Fetuses received, intravenously, boluses of adrenocorticotropic hormone at 2 doses, and plasma samples were obtained for analysis of the cortisol response. This stimulation by adrenocorticotropic hormone was then repeated in the same fetuses approximately 4 days later, after the increase of resting daily cortisol values in one but not the other fetus. Results: Cortisol responses to adrenocorticotropic hormone before changes in daily resting cortisol concentrations were indistinguishable between twins. However, after separation of daily resting cortisol values, fetuses in group A (elevated resting cortisol concentration) demonstrated a significantly increased response to stimulation by adrenocorticotropic hormone. Conclusion: These results suggest a differential development in response to stimulation by adrenocorticotropic hormone between twin fetuses in vivo as the mechanism responsible for the asynchronous elevation of one twin’s resting plasma cortisol concentration. (Am J Obstet Gynecol 1999;181:498-502.)

Stress response to chronic inflammation in the horse.

Five clinically healthy Thoroughbred geldings were injected with Freund's adjuvant 3 times to induce a chronic inflammatory response. Blood was collected at various times before and after adjuvant administration. Clinical responses (rectal temperature and general demeanor) were also monitored. Adjuvant injection induced increases in rectal temperature and plasma fibrinogen concentration (maximum levels measured were mean +/- s.d. 39.7 +/- 0.5 degrees C and 8.2 +/- 0.3 g/l, respectively), indicative of an inflammatory response. A mild clinical depression was also observed in the horses for 24 h after the first injection of adjuvant only. Plasma cortisol levels decreased significantly from control levels of mean +/- s.d. 187.7 +/- 24.3 nmol/l to a minimum of 80.2 +/- 22.1 nmol/l (P < 0.01) 9 days after the first injection of adjuvant. Conversely, plasma insulin levels increased after the first injection of adjuvant to a maximum (96.7 +/- 15.2 iu/ml; P < 0.01) 12 days later, while plasma glucose concentrations tended to decline. A control group of horses to rule out contemporary environmental influences on the physiological and biochemical indices measured was not included in this study. The results show that chronic inflammation in the horse depressed resting plasma cortisol concentrations.

Primary and secondary stress responses to line capture in the blue mao mao

Primary and secondary stress responses were measured in wild Scorpis violaceus subjected to burst swimming from angling. Fish were blood sampled from 20 s to 30 min after hooking. Consequent rises in plasma adrenaline (14–316 nmol l−1), noradrenaline (25–345 nmol l−1), and cortisol (0.4–197 ng ml−1) correlated with time since capture, and plasma lactate (0.1–12.2 mmol l−1) reflected work done during intense exercise. Haemoglobin concentration and haematocrit also increased with exercise, and erythrocyte swelling occurred. Wild S. violaceus demonstrated a spontaneity and intensity of exercise not seen in fish acclimatized to aquarium conditions. By contrast, the stress responses of fish in captivity, despite careful husbandry, differed qualitatively and quantitatively from those in the wild. Cannulated fish had higher resting plasma cortisol concentrations (61.9±9.5 ng ml−1) than did rapidly caught wild fish (&lt;5 ng ml−1) and these values were not significantly changed with burst swimming. Catecholamine secretion, possibly suppressed by cortisol, was insufficient to cause erythrocyte swelling. Erythrocyte nucleotides do not play a role in exercise, but are elevated in captive fish. It is hypothesized that primary endocrine responses are triggered by higher cortical processing of sensory information which is fundamentally different in the natural environment.

Primary and secondary stress responses to line capture in the blue mao mao

Primary and secondary stress responses were measured in wild Scorpis violaceus subjected to burst swimming from angling. Fish were blood sampled from 20 s to 30 min after hooking. Consequent rises in plasma adrenaline (14–316 nmol l−1), noradrenaline (25–345 nmol l−1), and cortisol (0.4–197 ng ml−1) correlated with time since capture, and plasma lactate (0.1–12.2 mmol l−1) reflected work done during intense exercise. Haemoglobin concentration and haematocrit also increased with exercise, and erythrocyte swelling occurred. Wild S. violaceus demonstrated a spontaneity and intensity of exercise not seen in fish acclimatized to aquarium conditions. By contrast, the stress responses of fish in captivity, despite careful husbandry, differed qualitatively and quantitatively from those in the wild. Cannulated fish had higher resting plasma cortisol concentrations (61.9±9.5 ng ml−1) than did rapidly caught wild fish (<5 ng ml−1) and these values were not significantly changed with burst swimming. Catecholamine secretion, possibly suppressed by cortisol, was insufficient to cause erythrocyte swelling. Erythrocyte nucleotides do not play a role in exercise, but are elevated in captive fish. It is hypothesized that primary endocrine responses are triggered by higher cortical processing of sensory information which is fundamentally different in the natural environment.

Cortisol, testosterone, and insulin action during intense swimming training in humans.

An increase in the amounts of circulating plasma cortisol or a decrease in testosterone can result in whole-body insulin resistance. The purpose of this study was to determine if the increase in cortisol and/or decrease in testosterone concentrations commonly evident with intense endurance training is associated with insulin resistance. Male (n = 9) and female (n = 10) swimmers were examined during the off-season, after 9 weeks (9 WKS) of training averaging 5,500 m* day(-1) and after an additional 9 weeks (18 WKS) of training averaging 8,300 m*day(-1). Resting plasma cortisol concentration was (P < or = 0.05) higher in the women compared to the men at 9 WKS; values were not significantly different between genders at 18 WKS. Plasma testosterone concentration decreased significantly (P < or = 0.05) in the men at 9 and 18 WKS, but did not change in the women. Whole-body insulin action, as determined by insulin and glucose responses during a 120 min, 75-g oral glucose tolerance test, did not change with training in either the men or women. These data indicated that plasma testosterone concentration can decrease in male swimmers during intense endurance training; this alteration does not affect wholebody insulin action. There would also appear to be a gender-specific response of plasma cortisol to endurance training, which does not influence insulin action.

Genetic, Environmental, and Interaction Effects on Growth and Stress Response of Chinook Salmon (Oncorhynchus tshawytscha) Fry

Eight full- and half-sib families of chinook salmon (Oncorhynchus tshawytscha) were held during egg development at two temperatures (8.0 and 10.2 °C). As fry, these families were measured for relative growth rate, initial and final wet weight, hematocrit values before and 2 h after a 30-s handling stress, and plasma cortisol and glucose concentrations before and after stress. Significant sire effects were found for all measured traits, and significant dam effects were found for all traits except for the poststress increases in cortisol concentrations. There were significant genotype-by-environment interactions for all traits except unstressed (control) plasma glucose concentrations. Incubation temperature had a significant effect on relative growth rate and final wet weight only. We found a significant correlation between poststress plasma glucose concentration and relative growth rate for all fish, independent of family, while resting plasma cortisol concentration and poststress hematocrit correlated with wet weight only when analyzed within the eight individual families. Genetic contributions to stress-related parameters and genotype-by-environment interactions should be considered as a factor in stress-related research with fish.

Effects of xylazine on the stress response to transport in male goats

A 20-min van journey increased plasma cortisol concentrations to 15–25 ng/ml in male goats, blood glucose concentrations were not affected, but respiratory rates and heart rates were increased, the latter by 40 beats per min. A 2-h van journey increased plasma cortisol to >25 ng/ml and blood glucose to >5 mmol/l. Respiratory rates were increased to >40 breaths per min and heart rates by >100 beats per min. Xylazine alone (0.01 mg/kg) suppressed resting plasma cortisol concentrations, increased blood glucose concentrations to 4.5 ± 0.8 mmol/l and suppressed respiratory rates by 5–10 breaths per min and heart rates by 20 beats per min. Cortisol concentrations were suppressed by xylazine treatment if given before a 20-min van journey, and for approximately 60 min if given 20 min after the start of a 2-h journey. When combined with transport, xylazine caused an additive effect on glucose concentrations, but suppressed respiratory and heart rates. However, for the latter criteria the timing of suppression was different depending on the time of onset and duration of the stressor. Injection of 50 μg ovine corticotrophin releasing factor (CRF) caused an immediate elevation of cortisol concentrations (but not glucose) which lasted for at least 6 h compared with the return to baseline within 60 min after either length of journey. Xylazine pretreatment did not alter the cortisol response to CRF, suggesting that xylazine must act centrally above pituitary level when blocking the cortisol response to transport. It is proposed that under resting conditions the hypothalamus is under alpha 2-adrenergic suppression. Stimulation of cortisol secretion in response to a stressor can be inhibited by an alpha 2-adrenergic agonist.

The effect of pregnancy on metabolic responses during rest, immersion, and aerobic exercise in the water

To examine the effects of advancing pregnancy on metabolic responses, 12 women, who were recruited early in pregnancy, were studied during 20 minutes of immersion in 30° C water, followed by 20 minutes of exercise in the water (60% of predicted maximal capacity) and 20 minutes of lateral supine recovery. Each subject completed the trials during the fifteenth, twenty-fifth, and thirty-fifth weeks of pregnancy, as well as a control period 8 to 10 weeks post partum. Resting oxygen uptake increased with advancing pregnancy. Resting oxygen uptake was higher in the water than on land but was not altered by pregnancy. Exericse oxygen uptakes were similar for all trials, but the work load required to elicit the VO2 decreased during the thirty-fifth week of pregnancy. Exercise heart rates followed the same pattern as oxygen uptake. Lactate concentrations declined with advancing pregnancy after exercise. Blood glucose levels were normal for pregnancy but declined slightly during exercise. Blood triglyceride levels were elevated with exercise, with a tendency to increase with advancing pregnancy. Resting plasma cortisol concentrations increased with pregnancy but remained lower during immersion and exercise. These results suggest that pregnancy significantly alters metabolic responses to exercise in the water.

Effects of megestrol acetate on glucose tolerance and growth hormone secretion in the cat

Long-term administration of relatively high therapeutic dosages of megestrol acetate to cats produced a progressive deterioration in glucose tolerance, with a significant (P less than 0.05) increase in mean fasting plasma glucose concentrations and decrease in mean plasma glucose clearance rates after six and 12 months of treatment. There appeared to be no relationship, however, between the development of glucose intolerance and circulating growth hormone (GH) concentrations in the cats of this study, since no significant rise in plasma GH concentrations was detected during the 12 month period of megestrol acetate treatment. Administration of megestrol acetate also produced a progressive decrease in both resting plasma cortisol concentrations and cortisol concentrations after ACTH stimulation. Three months after discontinuation of megestrol acetate, the elevated fasting plasma glucose concentrations, decreased glucose clearance rates and subnormal plasma cortisol concentrations all returned to normal pretreatment values, indicating resolution of glucose intolerance and hypoadrenocorticism. The results of this study demonstrate that administration of megestrol acetate to cats can produce a state of moderate to severe glucose intolerance, which is usually reversible after cessation of treatment. Although the exact mechanism of the glucose intolerance and overt diabetes mellitus induced by progestagen treatment of cats remains unclear, it is likely that these alterations in glucose metabolism result primarily from the glucocorticoid activity intrinsic to megestrol acetate.

Cortisol Secretion Rate in Gonadectomized Female Sockeye Salmon (Oncorhynchus nerka): Effects of Estrogen and Cortisol Treatment

Gonadectomized female sockeye salmon (Oncorhynchus nerka) were injected intramuscularly with cortisol, estradiol, estradiol cypionate, or peanut oil for 8 weeks. The metabolic clearance rate of cortisol was determined by the single injection technique and calculated from the formula for a two pool system. The cortisol secretion rate was determined from the metabolic clearance rate and the plasma cortisol concentration.The volume of distribution of cortisol in the inner compartment (V1) and the outer compartment (V2), the metabolic clearance rate (MCR), the resting secretion rate (S), and the resting plasma cortisol concentration were all significantly higher in the estradiol-injected group than in the peanut oil-injected control group, and the plasma cortisol concentration at the end of the experiment was lower. V1, MCR, and S were also significantly higher in the estradiol cypionate-injected group. There were no significant differences between the cortisol-injected group and the peanut oil-injected control group or in the biological half life of cortisol between any groups.There were no significant changes in the red colour of the flesh or in body weight during the experiment. However, the cortisol-injected group did show the largest weight loss.