Changes In Serum Cortisol Levels Research Articles

Cushing disease: use of perioperative serum cortisol measurements in early determination of success following pituitary surgery

✓Despite many recent advances, management of cases of Cushing disease continues to be challenging. After complete resection of ACTH-secreting adenomas, patients develop transient ACTH deficiency requiring glucocorticoid replacement for several months. The current recommendation by many centers, including ours, for patients with ACTH-secreting adenomas is to withhold glucocorticoid therapy during and immediately after adenomectomy until there is clinical or biochemical evidence of ACTH deficiency. A serum cortisol level of less than 2 μg/dl within the first 48 hours after adenomectomy is a reliable biochemical marker of ACTH deficiency and is associated with clinical remission of Cushing disease. Higher serum cortisol levels in the immediate postoperative period should be interpreted with caution. The decision to immediately reexplore the sella turcica should be individualized, taking into account the findings at surgery, the histopathological findings, and the changes in serum cortisol levels as well as the patient's wishes and concerns. Optimal diagnosis and therapy for patients with Cushing disease require thorough and close coordination and involvement of all members of the management team.

Temporary adrenal dysfunction with descending thoracic aortic occlusion

Background. We sought to determine whether descending thoracic aortic occlusion (DTAOC) induced ischemia results in adrenal dysfunction. Methods. Eight pigs underwent DTAOC for 45 min. Six control pigs underwent a sham procedure. Serum cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline, at the end of DTAOC, 30 and 60 min after restoration of flow, and 24 hours later. Statistical analysis was performed using repeated measures ANOVA and t-test. Results. In the study group, cortisol levels decreased during DTAOC (p=0.048) and 30 min after flow restoration (p=0.004). In the control group there was no change in serum cortisol levels. In the study group the drop in serum cortisol was associated with an increase in ACTH levels during DTAOC (p=0.040) and 30 minutes after flow restoration (p=0.070). The increase in ACTH was also significant when compared to the controls during DTAOC (p=0.030) and 30 min after blood flow restoration (p=0.040). Conclusions. There is a transient period of adrenal dysfunction associated with DTAOC that results in stimulation of the pituitary-adrenal axis.

Low‐dose ACTH (1 µg) salivary test: a potential alternative to the classical blood test

Salivary cortisol is unaffected by cortisol binding globulin (CBG) and hence allows CBG-related variations in serum total cortisol to be bypassed. We assessed whether or not salivary cortisol can be used for the low-dose (1 microg) ACTH test in subjects with presumed normal and elevated levels of CBG. We measured serum and salivary cortisol responses to intravenous administration of 1 microg ACTH in 14 healthy volunteers, 14 'hyperoestrogenic' women [in their first or early second trimester of pregnancy, using oral contraceptives (OC) or on hormone replacement therapy (HRT)] and 10 patients with secondary hypoadrenalism. Cortisol levels were recorded before as well as 30 and 60 min (+30; +60 min) after ACTH administration. Baseline salivary cortisol did not differ significantly between the hypoadrenal and healthy patients (7.11+/-1.4 and 12.13+/-1.59 nmol/l; P=0.48) but there was a significant difference between hypoadrenal and hyperoestrogenic patients (18.94+/- 3.44 nmol/l; P=0.01). The largest difference between hypoadrenal patients and healthy individuals was observed at+30 min (9.16+/-2.8, 52.65+/-8.78 and 48.81+/- 6.9 nmol/l, in the hypoadrenal, healthy and hyperoestrogenic patients, respectively; P< 0.05). At this time-point values< 24.28 nmol/l were found in all hypoadrenal patients and cortisol levels >or= 27.6 nmol/l were found in 26 out of 28 healthy volunteers. ACTH-stimulated serum cortisol but not salivary cortisol was significantly higher in hyperoestrogenic women than in the healthy volunteers at either+30 or+60 min. The salivary low-dose ACTH test yields results that parallel the response of circulating cortisol to ACTH and may provide an alternative to the blood test, particularly in situations where increased CBG levels complicate the changes in serum cortisol levels.

Effects on Hippocampus of Lifelong Absence of Glucocorticoids in the Pro-Opiomelanocortin Null Mutant Mouse Reveal Complex Relationship Between Glucocorticoids and Hippocampal Structure and Function

In humans changes in serum cortisol levels have been observed with aging, stress, and with affective disorders such as major depression and post-traumatic stress disorder. Corticosteroids are known to influence hippocampal structure and function; specifically, plasma corticosteroid levels have been inversely correlated with hippocampal cell proliferation, cell death, and impaired memory function. The relationship between corticosteroids and structure and function of the hippocampus has been studied in experimental systems in adult animals by increasing or decreasing corticosterone levels through pharmacological supplementation and through surgical removal of the adrenal gland. Here, we utilized the genetically engineered pro-opiomelanocortin (POMC) null mutant mouse, which because of the lack of all POMC peptides has no corticosterone from birth throughout life. The effect of this lifelong absence of corticosterone on the dentate gyrus of the hippocampus is a decrease in granule cell density, which correlated with a decrease in cell proliferation but not an increase in cell degeneration. Fine morphology of granule cells was unaltered. Analyses of gene expression revealed no changes in POMC null mutant vs wild-type hippocampus with respect to levels of expression of corticoid receptor genes or genes known to be regulated by corticosterone. Spatial learning as tested by the Morris water maze was not altered in the POMC null mutant mouse. Taken together with findings from other studies of the effects of altered levels of corticosteroids on the hippocampus, our results argue for a complex homeostasis in which disturbances of any one factor can offset the system in varying ways.

Stress in wild-caught Eurasian otters (Lutra lutra): effects of a long-acting neuroleptic and time in captivity

AbstractAs part of a translocation project, 28 Eurasian otters (Lutra lutra) were captured from the wild and transported to the Barcelona Zoo for veterinary evaluation, quarantine and intraperitoneal implantation of telemetry devices. Eleven animals were injected with the long-acting neuroleptic (LAN) perphenazine enanthate at the time of capture and the remaining animals served as a control group. During their time in captivity, which averaged 23 days, all of the animals were bled three times. Haematological and biochemical parameters were evaluated, including red blood cell count (RBC), haemoglobin (Hb), white blood cell count (WBC), blood urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), lactate dehydrogenase (LDH), creatine kinase (CK), albumin, and serum cortisol. No significant differences were found between treated and control otters except for monocyte count, which was higher in treated animals. Time after capture had an effect on many parameters. RBC and Hb decreased at first and then increased, while WBC and segmented neutrophils decreased over time. Most of the biochemical parameters considered to vary in relation to stress, including AST, ALT, CK, AP and LDH, decreased over time, suggesting that the stress responses of the animals decreased throughout the period of captivity. However, no significant change in serum cortisol levels was noted. The lack of effect of perphenazine treatment on haematological parameters should encourage further research on other stress indicators applicable to wild animals, such as behaviour or faecal cortisol concentration. Finally, the results obtained in this study suggest that, when captive conditions are adequate, keeping wild-caught animals in human care for a period of time prior to their release into the wild can be beneficial. However, further studies taking into account other welfare indicators would be useful.

Effect of High Starting Dose of Budesonide Inhalation Suspension on Serum Cortisol Concentration in Young Children with Recurrent Wheezing Episodes

Introduction. There are no available data on the safety of recommended schedules for the initiation of treatment with budesonide inhalation suspension in children with recurrent wheezing episodes. We compared the safety of high and low starting dose of budesonide by measuring their effect on plasma cortisol concentration. Methods. A randomized double-blind, placebo-controlled design was used. Twenty-nine children ages 6 months to 3 years were divided into three groups: (1) high starting dose: 1 mg budesonide inhalation suspension twice daily followed by a stepwise decrease of 25% every second day for 8 days (n = 11); (2) low starting dose: 0.25 mg twice daily for 8 days (n = 11); (3) placebo (n = 7). The 8 AM (fasting) and 1-hour post-ACTH stimulation plasma cortisol concentrations were measured before and 10 days after initiation of budesonide treatment. Results. Before treatment and after 8–10 days of treatment, there was no significant difference in mean serum cortisol concentration in the high starting dose, low-dose and placebo groups, either at 8 AM or at 1 hour after ACTH stimulation. Conclusion. The administration of nebulized suspension of budesonide at a high starting dose (2 mg/day for 2 days) followed by a rapid stepwise decrease over 8 days was safe, causing similar changes in serum cortisol levels to low-dose budesonide suspension or placebo.

Equivalence of Two Steroid-Containing Inhalers: Easyhaler Multidose Powder Inhaler Compared with Conventional Aerosol with Large-Volume Spacer

Background and Objectives: An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 μg of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. Methods: One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. Results: Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. Conclusion: It was concluded that the devices tested were equivalent in terms of efficacy and safety.

Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide nebulizing suspension in young children with recurrent wheezing episodes

Background: There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes. We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose. Methods: In a double-blind design, 42 children aged 6 months to 3 years were randomly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25% every second day for 1 week (group A) or a low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test. Results: The two groups were comparable for all parameters evaluated. During the first week of treatment, there was a significant decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing ( p = 0.0001), 39% for diurnal cough ( p = 0.036), and 39% for nocturnal cough ( p = 0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in group B ( p = 0.02). This early improvement was sustained for the rest of the follow-up period. The high dose starting schedule was not associated with any change in serum cortisol level. Conclusions: The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid (1 week) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels.

Acute effects of exercise at low altitude (350 meters below sea level) on hormones of the anterior pituitary & cortisol in athletes.

The purpose of this study was to examine the effects of exercise on anterior pituitary hormones (adrenocorticotropic hormone (ACTH), leutinizing hormone (LH) and growth hormone) as well as on cortisol at low altitude (350 meters below the sea level) and to compare these effects with those at a moderate level altitude (620 meters above the sea level). Ten male athletes with running experience participated in a 21-Km competitive race. Serum levels of ACTH, LH, growth hormone and cortisol were measured before and after the race at each of the altitudes. A significant increase in the serum levels of ACTH and growth hormone were observed in response to this exercise at low altitude. Similar exercise at 620 meters above the sea level resulted in a significant increase only in the serum levels of growth hormone. Serum levels of LH were not affected by this kind of exercise at both altitudes. Serum cortisol levels were increased following exercise at both altitudes. Altogether, these observations show a differential response of the anterior pituitary to exercise at low and normal altitudes. These data suggest that ACTH may have a role in the acclimatization to exercise at low altitudes. The role of growth hormone and LH in this conditioning process seems to be insignificant. The changes in serum cortisol levels in response to exercise at both altitudes correlate well with the effect of exercise on energy metabolism.

Relationship between Social Factors and Pituitary-Adrenocortical Activity in Female Rhesus Monkeys ( Macaca mulatta)

Psychosocial stress in humans has been related to the occurrence or progression of certain diseases and a positive social environment has been shown, in some cases, to ameliorate this effect. In many experimental studies changes in serum cortisol levels have been used as an endocrine-defined stress response, however, the variation in this measure under unchanging conditions in socially housed animals is not well documented. The present study was designed to examine the relationship between specific social behaviors and concentrations of serum cortisol in female rhesus monkeys. Subjects were members of one of two social groups. One was an established long-term (8 years) group with members which had from one to many kin, while the second was a group formed 5 months prior to the onset of the present study composed of initially unfamiliar animals. Blood samples were collected weekly and a total of 16 hr of behavioral data was collected on each subject. For purposes of analyses, the year-long study was organized according to calendar quarters (3 months) with cortisol concentrations averaged and behavioral categories cumulated. When regression techniques were applied, it is of note that neither group nor dominance rank was a predictor of cortisol levels. However, when a correlation analysis was applied to each group separately to assess the effect of dominance rank, rank significantly correlated with cortisol levels in the established but not in the recently formed group. In each quarter, analyses revealed behavioral categories which combined to account for a significant proportion of the variance in cortisol levels, but these behaviors were not identical over the four quarters. For three of the four quarters analyzed, and for the year as a whole, an affiliative behavioral category was predictive of cortisol levels in addition to agonistic behavioral categories. These data suggest that cortisol levels are influenced by not only negative interactions, such as receiving bites, but also by positive interactions such as receiving grooms. Results also showed that reconciliatory behaviors occurred significantly more frequently following dyadic agonistic episodes in the recently formed versus the long-term group. The higher rate of reconciliatory behaviors exhibited by the recently formed group may account for the lack of a dominance rank/cortisol relationship.

Adrenocortical Function in Patients investigated for Active Tuberculosis

Previous reports have identified adrenal insufficiency in groups of patients with active pulmonary tuberculosis. To investigate this possibility, serum cortisol levels were measured in consecutive patients admitted to the hospital for investigation of active tuberculosis. Blood was drawn for cortisol determination promptly at the time of hospital admission, in the morning and afternoon before commencing chemotherapy for the suspected tuberculosis, and before the diagnosis was confirmed. Thirty-seven patients were assessed; 19 of these patients were subsequently proven to have active pulmonary tuberculosis, six had pulmonary disease caused by mycobacteria other than tuberculosis, and 12 had radiologic appearance indicating tuberculosis, accompanied by a significant tuberculin skin reaction but with negative sputum cultures and no change in roentgenographic appearance during the course of treatment. In evaluating the adrenocortical function, the morning and afternoon serum cortisol level was measured and the diurnal change in serum cortisol level (the difference between afternoon and morning levels) was calculated. There was no association of either morning cortisol levels or diurnal change in cortisol levels with age, gender, or race. There was no difference among the three groups in either cortisol determination. Although difference in morning cortisol levels between those with extensive as compared with limited disease was not statistically significant (p = 0.349 from analysis of variance), there was a significantly decreased diurnal change in cortisol levels in those with extensive disease as compared with those with limited disease (+2.7 +/- 188.3 vs -259.1 +/- 177.1). We conclude that patients in our hospital with active pulmonary tuberculosis do not exhibit decreased adrenocortical function as compared with groups of patients without active pulmonary tuberculosis.

Effects of Rearing Density on the Stress Response and Growth of Rainbow Trout

One-year-old rainbow trout Oncorhynchus mykiss were reared for 8 weeks at a density of either 56 or 267 g fish/L (based on the volume of net-pens), equivalent to density indexes of 2.3 and 11.1 g fish/L-cm total fish length), respectively. The fish were held in 0.6 × 0.3-m netpens submerged to a depth of 0.15 m. Two net-pens for each fish density were suspended in each of three 3,040-L circular tanks provided with sufficient flow to maintain loading rates in the tanks at less than 800 g/(L-min). The fish were then subjected to an acute handling stress by being removed from the water for 60 s. No differences in the time course of changes in serum cortisol levels or hematocrits were observed over a 12-h period between fish in the two density groups. There were also no differences between the two groups of fish in weight, length, body condition factor (weight/length3), interrenal nuclear diameter, or the percentage of the anterior stomach that was mucosa. These results indicate that if high water quality is maintained, 1-year-old rainbow trout can be reared at a density index as high as 11. 1 g/(L-cm) without impairing their growth or causing overt chronic stress.

Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects

To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 μg bid), high dose beclomethasone aerosol (1000 μg bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV 1) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (±SE) value of FEV 1 4 h after exposure to TDI was 2.6 ± 0.17 L, which went to 3.3±0.12 after low dose beclomethasone, and to 3.5±0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV 1 in the 8 h after exposure to TDI, between treatments: F = 9.87, (P < 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD 20 decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD 20 decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63). By contrast, airway responsiveness to methacholine did not change 8 h after exposure to TDI in subjects treated with high dose inhaled beclomethasone: the PD 20 was 0.78 mg (GSEM, 1.51) before and 0.71 mg (GSEM, 1.58) after exposure to TDI. The protective effect of beclomethasone was obtained without side effects and without changes in serum cortisol levels (08.00) in any of the nine examined subjects. These results suggest that the inhibitory effect of inhaled beclomethasone on TDI-induced late asthmatic reactions and increased responsiveness is dose-dependent.

Effect of adrenal steroids on testosterone and luteinizing hormone secretion in the ram.

The effects of adrenal steroids on testosterone and LH secretion and changes in serum cortisol levels in response to treatments were studied in the ram. Acute administration of synthetic ACTH (10 micrograms/kg BW) elevated (P less than 0.01) serum cortisol and transiently suppressed (P less than 0.05) serum testosterone and LH. Acute dexamethasone treatment suppressed (P less than 0.01) serum cortisol, testosterone and LH. Administration of vehicle had no effect (P greater than 0.10) on serum hormone levels. These data support the contention that adrenal steroids inhibit testicular endocrine function indirectly by acting at the hypothalamic or pituitary level because both ACTH and dexamethasone treatments suppressed serum LH. To differentiate between hypothalamic and pituitary sites of action, the pituitary and testicular responses to an LHRH challenge (100 micrograms) were examined in rams chronically treated with dexamethasone (5 mg i.m., twice daily for 5 days). This treatment regimen suppressed (P less than 0.01) serum cortisol levels. Compared with controls, basal testosterone levels were suppressed (P less than 0.05) in dexamethasone-treated rams; however, no effect (P greater than 0.10) on the magnitude of the testosterone response to LHRH or on either basal or LHRH-stimulated LH secretion was observed. Thus, although a direct testicular effect cannot be eliminated, these data suggest that, in the ram, adrenal steroids inhibit testicular endocrine function by action at the level of the hypothalamus.

Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners

Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 μg intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 μg intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were simiiar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We conclude that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in “stress-induced” or “psychogenic” amenorrhea.

Male endocrine responses to females: Effects of social cues in cynomolgus macaques.

This study tested the hypothesis that the hormonal responses of male macaques to sexually receptive females are mediated by specific socioenvironmental cues. Twelve, socially living male Macaca fascicularis were exposed to two-ovariectomized, estrogen-primed females under pair test, peer group, and peer group without dominant male conditions. Preexposure to postexposure changes in serum cortisol levels and testosterone levels were examined in relation to male dominance rank, age, and conditions of access to stimulus females. The males displayed significantly lower cortisol increases and greater testosterone increases with females under peer group than pair test conditions. Dominant males displayed greater testosterone increases than subordinate males under peer group conditions. The testosterone levels of subordinate males were greatly enhanced by removing the dominant male from each group. Adult males displayed greater cortisol responsivity to changes in conditions of access to females than did subadult males. Subadult males displayed greater testosterone responsivity to removal of the dominant male from the group than did adult males. It is concluded that specific social cues can greatly influence the endocrine responses of males to receptive females, and further, that there may be optimal socioenvironmental parameters for eliciting testosterone increases in male primates.

Factors Regulating Levels of Cortisol in Cerebrospinal Fluid of Monkeys during Acute and Chronic Hypercortisolemia

Cortisol levels in the serum and cerebrospinal fluid (CSF) were studied in ovariectomized, estrogen-treated monkeys during either prolonged hypercortisolemia or the more transient effects of a bolus injection of cortisol. Control (saline-treated) animals showed the expected diurnal rhythm in serum cortisol, but proportionately more cortisol was present in the CSF when serum levels were high (i.e. in the morning). Prolonged hypercortisolemia for up to 37 days was produced by either thrice daily injections of cortisol itself or single daily injections of ACTH1-24 in the morning. Both treatments produced disproportionately larger amounts of cortisol in the CSF than in the serum, and the CSF/serum cortisol ratio was increased. Furthermore, prolonged ACTH treatment caused a marked elevation in CSF cortisol in afternoon samples taken at 16.30 h compared with those at 10.00 h, in the absence of a similar change in serum cortisol levels. The relative importance of entry and clearance of cortisol in the CSF in these conditions was studied in several ways. 'Free' cortisol levels in serum (determined by equilibrium dialysis) were equal to CSF cortisol levels in control monkeys, but were less than those in the CSF of hypercortisolemic animals. Entry of cortisol into CSF after a bolus injection was rapid, but, unlike serum, CSF cortisol levels did not decline significantly over a 70-min sampling period and the delayed clearance from the CSF could account for some of the effects seen during hypercortisolemia. Neither high levels of prolactin (which is elevated together with cortisol in 'stress'), induced by giving sulpiride, nor treatment with progesterone (which is also bound by corticosteroid binding globulin) altered the distribution of cortisol between blood and CSF. The concentrations of cortisol in the CSF therefore are regulated by factors influencing both its entry and clearance from the cerebral compartment. Neural tissues sensitive to cortisol are thus exposed to levels of this hormone that are both qualitatively and quantitatively different from those expected by direct extrapolation from serum levels.

Sodium metabolism of the freshwater cyprinodont,Fundulus catenatus

1. Transfer of the freshwater cyprinodont,Fundulus catenatus, into 40% sea water caused a slow rise in serum sodium levels, total body sodium, and the rate of sodium efflux. 2. Serum sodium levels were first reduced by expanding sodium space. In some cases the animals eventually brought sodium parameters (except efflux) back to fresh water levels; in other cases the sodium space remained expanded. 3. Transfer of animals adapted to 40% sea water on to 52% or 65% sea water caused a second rise in the sodium load and expansion of the sodium space. The animals could not survive indefinitely in 65% sea water. 4. Water permeability first decreased, and then increased after transfer into saline. The chenges in water permeability correlated roughly with changes in serum cortisol levels. 5. The animals remained hyposmotic to the environment in both 40% and 65% sea water and drank sufficient sea water to stay in positive water balance. They were not able carry out a net excretion of sodium in salinities above 40% sea water.