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Biomedical subjects

E O Johnson

Publications and source records attributed to E O Johnson.

At least 19 recordsLinked to original sources
PubMed1996

The biobehavioral consequences of psychogenic stress in a small, social primate (Callithrix jacchus jacchus).

The biobehavioral consequences of psychogenic stress were examined using neuroendocrine and ethological methods in a captive colony of common marmosets (Callithrix jacchus jacchus). Specifically, hypothalamic-pituitary-adrenal (HPA) axis reactivity was evaluated as a function of gender and social status in four consecutive social environments [(1) stable heterosexual pairs; (2) isolation; (3) unstable peer groups; and (4) stable peer groups], by measuring both basal plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropin-releasing hormone (oCRH), and ACTH1-24. Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and/or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism.

Adrenocorticotropic Hormone↗
PubMed1996

Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in a glucocorticoid resistant nonhuman primate.

Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal axis through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are a New World primate characterized by extraordinarily high levels of circulating ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to their massive levels of glucocorticoids was attributed to a decreased affinity of their GR for glucocorticoids, as well as a compromised ability of this receptor to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid excess, on the other hand, was attributed to a renal MR which responded poorly to cortisol, but normally to aldosterone. The purpose of this study was to examine MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus) hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in all of the hippocampal subfields of the marmoset, and this was obvious in rough comparisons with those of a typical glucocorticoid-sensitive Old World primate, the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density distribution of the marmoset also appeared to differ from that in the rhesus and from those previously reported in rats and humans. These findings suggest that there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus, which appears to be the result of target tissue resistance to glucocorticoids and inappropriate down-regulation by the elevated, but ineffective, circulating cortisol.

Animals↗
PubMed1996

Indicators of genetic and environmental influences in drug abusing individuals.

To assess relative contribution of genetic and environmental influences in individual cases of drug abuse/dependence, separate scales were constructed from DIS (version III) drug symptom items. Using data from 38 MZ and 35 DZ male twin pairs, items with significant MZ/DZ differences in probandwise concordance were assigned to a genetic scale whereas items without significant MZ/DZ differences were assigned to an environmental scale. As expected, significant differences were found between MZ and DZ twins in intraclass correlations for the genetic but not environmental scale. Genetic scores on drug and alcohol scales were correlated (r = 0.40), whereas environmental scales were not. When scores on the genetic scales were compared, the correlation between drug and alcohol scores within individuals was similar to that across MZ twins, both of which were higher than the correlation across DZ twins. These results suggest (1) relative contribution of genetic and environmental influences in individual cases of drug dependence can be assessed, and (2) common genetic mechanisms may be involved in alcohol and drug dependence.

Adolescent↗
PubMed1996

Indicators of genetic and environmental influence in alcohol-dependent individuals.

Although much is known about genetic and environmental influences in alcohol dependence at the population level, little is known about the relative contribution of such influences on individuals. As an initial step toward individual assessment, concordance for the Diagnostic Interview Schedule, version III alcohol symptoms was determined in a sample (n = 113) of male monozygotic (MZ) and dizygotic (DZ) twins. Items were assigned to a genetic or environmental scale on the basis of significant MZ/DZ differences in proband-wise concordance rates. Weights were assigned to items based on factor analyses. For the genetic scale, significant differences were found between MZ and DZ intraclass correlations. No significant differences were found between MZ and DZ correlations on the environmental scale. When scores on the environmental scale were controlled, genetic scale scores were correlated with earlier age of onset of alcohol problems and a shorter interval between first intoxication and onset of alcohol problems. When scores on the genetic scale were controlled, environmental scale scores were correlated with later age of onset of alcohol problems and a longer interval between first intoxication and onset of alcohol problems. These results suggest it is possible to assess relative influence of genetic and environmental factors in individual cases of alcohol dependence.

Alcoholism↗
PubMed1996

Subtypes of alcohol-dependent men: a typology based on relative genetic and environmental loading.

Using scales that distinguish between relative genetic and environmental loading, cluster analysis was used to identify three subtypes of alcohol dependence in Caucasian men from the Epidemiologic Catchment Area study (n = 911). Although all subjects met DSM-III criteria for alcohol dependence, only the severe subtype showed evidence of substantial genetic influence. When compared on a range of clinical characteristics, the mild subtype (53% of the sample) was typically least adversely affected and the severe subtype (17%) most affected, with the dyssocial subtype (30%) falling between. Severe subtype subjects had significantly greater comorbid drug dependence and were at least four times more likely than mild subjects to have sought treatment for alcohol problems. Ratio of genetic scale score to total symptom count (genetic ratio) was highest for the severe subtype (mean = 0.37), and negatively correlated with age of first alcohol problem (rs = -0.16) and years between first intoxication and first problem (rs = 0.19). No significant correlations were found between these clinical features and genetic ratio for the mild or dyssocial subtypes. Use of these scales and subtypes may improve our ability to detect specific gene effects in genetic linkage studies and to identify environmental influences in behavioral and epidemiological studies.

Adult↗
PubMed1996

Effects of early parenting on growth and development in a small primate.

We report here a study of the impact of caregiver-infant relationships on physical growth and behavioral development in a small primate, the common marmoset. Somatic growth was assessed from measurements of body weight, knee-heel length, head-tail length, head circumference, and pudendal pad width in females or testis volume in males obtained from unanesthetized monkeys. Behavioral information was gathered by focal animal samples for discrete rearing behaviors. Our data suggest that the frequency of positive parental behaviors during infancy is correlated with stature when the monkeys reach 10 and 20 wk of age. Furthermore, we found that juveniles that were mistreated by their parents during infancy were smaller in body weight, knee-heel length, and head-tail length, and they demonstrated abnormal social behavior. Finally, to address whether the apparent decreased growth observed in the young animals that had experienced negative parenting was also associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function, we examined the plasma ACTH and cortisol responses to synthetic ovine corticotropin-releasing hormone (oCRH) in these animals. We found that the incremental cortisol response to exogenous oCRH was significantly lower in the young adults that had experienced negative parenting during infancy compared with those who had nonabusive parents, indicating altered hypothalamic-pituitary-adrenal axis function in these animals. Our findings suggest that the quality of parental care influences later growth and behavior in the young marmoset.

Adrenocorticotropic Hormone↗
PubMed1996

Attitude and peer cross pressure: adolescent drug and alcohol use.

This research uses the concept of cross pressures, a concept created to explain political behavior, to predict the frequency of adolescent alcohol, cigarette, and drug use. Using a population of eighth, tenth, and twelfth graders from 207 Michigan public school districts, respondents reported their frequency of alcohol, cigarette, and drug use for thirty days and one year prior to the survey. They also reported their perception of friends' approval/disapproval of substance use, peer pressure to use, and their assessment of risk of use. Cross pressure patterns are created from these three variables and used to predict frequency of substance use. In addition to descriptive data and associations between independent and dependent variables, the findings show the patterns and extent of cross pressures to be highly predictive of frequency of substance use. The implications for understanding adolescent substance use and for educational programs are noted.

Adolescent↗
PubMed1996

The latent dimensionality of DIS/DSM-III-R nicotine dependence: exploratory analyses.

Decisions on DSM-IV criteria for alcohol dependence were based in part on latent structure analyses of field survey data on alcohol problems. Analogously, to investigate the latent structure of nicotine dependence in an epidemiological sample, we carried out a dichotomous item factor analysis of DSM-III-R symptom data gathered from 394 young adults who reported a history of sustained daily smoking. Smokers and their dependence symptoms were identified by means of the NIMH Diagnostic Interview Schedule version III revised, administered to a random sample of 1007 21-30-year-olds who were members of a health maintenance organization in the Detroit area. Comparing different latent structure models using LISCOMP software with bootstrap re-sampling, followed by multiple logistic regression, we found that a two-factor model indicating a 'general dependence' and a 'failed cessation' dimension best accounted for the observed data. Current smoking status (persistent vs. past smoking) was associated with the two factors independently. Replication and additional research on construct, discriminant and convergent validity are needed.

Adult↗
PubMed1995

Inhalants to heroin: a prospective analysis from adolescence to adulthood.

Recent cross-sectional studies have indicated that inhalant use might be a vulnerability marker for the development of heroin use. This study is the first prospective investigation of the hypothesized association between early inhalant use and later heroin use. Analyses were conducted using longitudinal data from a community sample of Woodlawn (an all African American community on the South side of Chicago). Six-hundred subjects participated in both the adolescent and the adult assessments (approximately ages 16 and 32, respectively). Youths with a history of inhalant use by age 16 were over nine times more likely to begin heroin use by age 32, even when other plausible risk factors for the development of heroin use were held constant (RR = 9.3; 95% C.I. = 1.3 - 51.3). These findings add to and are consistent with prior cross-sectional evidence from data based on treatment samples and national survey data. The results from this longitudinal assessment support the idea that youthful inhalant use should be regarded as a vulnerability marker for the development of more serious drug use involvement in the form of heroin use.

Administration, Inhalation↗
PubMed1995

Increased serum interleukin-1 beta during treatment of hyperthyroidism with antithyroid drugs.

Serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) levels were examined in patients with hyperthyroidism due to Graves' disease (GD) and toxic nodular goitre (TNG) before and during antithyroid drug therapy. A total of 32 patients were studied; 23 patients (14 with GD and nine with TNG) were in a hyperthyroid state (group A) and nine patients (four with GD and five with TNG) were in a euthyroid state, under carbimazole or methimazole treatment (group B). Ten hyperthyroid patients from group A (seven with GD and three with TNG) were also examined while euthyroid on treatment (Subgroup A). Serum was taken from all patients for the measurement of sIL-2R, IL-1 beta, total T4 (TT4), total T3 (TT3) and TSH concentrations. The results were compared with those from 30 normal controls. Serum sIL-2R levels were higher in Group A (671.3 +/- 74.0 U mL-1, mean +/- SE), than in Group B (214.1 +/- 61.8 U mL-1) and controls (149 +/- 14.8 U mL-1), P < 0.001. Similarly, the subgroup of 10 patients had higher levels of sIL-2R during the hyperthyroid phase than while euthyroid (P < 0.001). There was a positive correlation between sIL-2R values and levels of T4 and T3. In contrast, serum IL-1 beta levels were higher in Group B patients (197.5 +/- 39.2 pg mL-1) compared with those in Group A (66.5 +/- 17 pg mL-1, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The growth of conduct problem behaviors from middle childhood to early adolescence: sex differences and the suspected influence of early alcohol use.

OBJECTIVE: This study investigates the levels and rates of growth of conduct problem behaviors over time in an urban sample of American youth. Our hypotheses focused on differences between the sexes and between youths with and those without early use of alcohol without parental permission. METHOD: Data for this study are from an ongoing epidemiologic study of urban public school students, recruited originally at the time of their entry into Grades 1-2 between 1985 and 1987. Each spring, from 1991 to 1993, a total of 1,212 students were interviewed privately for this study. A total of 408 (54.2% female, 84.7% black) respondents met study criteria as either an "early unsanctioned alcohol user" or an "abstainer." These youths constitute the analytic subsample. RESULTS: Estimates from longitudinal growth modeling analyses showed that boys and girls had different initial levels of conduct problem behaviors, but similar rates of growth. Both the initial level of conduct problem behaviors and the rates of growth were greater for early unsanctioned alcohol users as compared to abstainers. In a combined analysis the difference between early unsanctioned alcohol users and abstainers seemed to offset the initially observed sex difference. CONCLUSION: Early alcohol use without parental permission was associated with higher levels of conduct problem behaviors by the ages of 10-12 years and higher rates of growth in those behaviors during the transition from late childhood to early adolescence for both boys and girls, although the levels differed by sex. It may be that unsanctioned early alcohol use puts youths on an accelerated pathway of conduct problem behaviors and development of conduct disorder in adolescence.

Adolescent↗
PubMed1992

Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis.

Environmental events, both physical and emotional, can produce stress reactions to widely varying degrees. Stress can affect many aspects of physiology, and levels of stress, emotional status, and means of coping with stress can influence health and disease. The stress system consists of brain elements, of which the main components are the corticotropin-releasing hormone (CRH) and locus ceruleus (LC)-norepinephrine (NE)/autonomic systems, as well as their peripheral effectors, the pituitary-adrenal axis and the autonomic system, which function to coordinate the stress response. Activation of the stress system results in behavioral and physical changes which allow the organism to adapt. This system is closely integrated with other central nervous system elements involved in the regulation of behavior and emotion, in addition to the axes responsible for reproduction, growth and immunity. With current trends in stress research which focus on understanding the mechanisms through which the stress-response is adaptive or becomes maladaptive, there is a growing association of stress system dysfunction, characterized by hyperactivity and/or hypoactivity to various pathophysiological states. The purpose of this review is to 1) define the concepts of stress and the stress response from a historical perspective, 2) present a dynamic overview of the biobehavioral mechanisms that participate in the stress response, and 3) examine the consequences of stress on the physiologic and behavioral well-being of the organism by integrating knowledge from apparently disparate fields of science.

Animals↗
PubMed1992

Cholecystokinin-octapeptide stimulates hypothalamic-pituitary-adrenal function in rats: role of corticotropin-releasing hormone.

Peripherally-administered cholecystokinin (CCK) is a profound suppressor of food intake, can promote anxiety, and causes the acute release of ACTH into plasma. Centrally administered corticotropin-releasing hormone (CRH), on the other hand, not only represents the principal stimulus to the pituitary corticotroph cell, but also has been shown to suppress appetite and to be profoundly anxiogenic. Because of the overlap in the effects of peripherally administered CCK and of centrally administered CRH, we report here a study to determine whether sulphated CCK octapeptide (CCK-8) could induce the release of CRH within the central nervous system. To accomplish this task, we first assessed the dose-related effects of CCK-8 on ACTH release. Graded doses of CCK-8 (0.1-10 micrograms/kg BW) given in an i.v. bolus to freely moving male rats, resulted in a dose-dependent increase of plasma immunoreactive (IR)-ACTH (ED50: 1-10 micrograms/kg BW). The lowest maximal stimulatory dose of CCK-8 (5 micrograms/kg BW) was used in all subsequent experiments. To evaluate whether CCK-induced ACTH secretion was mediated by a peripheral CCK receptor, an i.v. bolus injection of vehicle or L-364,718 (1 mg/kg BW), a specific, highly potent peripheral CCK receptor antagonist, was given before the i.v. administration of CCK-8 or vehicle. Plasma IR-ACTH response to CCK-8 was significantly attenuated by L-364,718. A role for the vagal afferents that contain CCK receptors in peripherally administered CCK-mediated hypothalamic-pituitary-adrenal (HPA) axis activation was examined in animals that had been pretreated with capsaicin, a potent neurotoxin that destroys vagal afferents. Plasma IR-ACTH and IR-corticosterone responses in capsaicin-treated animals were significantly lower than those in vehicle treated rats. In subsequent in vivo experiments, pituitary stalk-transected and sham-operated animals were used to evaluate whether CCK-8 stimulates the HPA axis via a centrally mediated mechanism. IR-ACTH and IR-corticosterone responses to i.v. CCK-8 were significantly reduced in the pituitary stalk-transected compared to sham-operated animals. In further effort to determine whether the central nervous system was involved in the plasma IR-ACTH response to the peripheral administration of i.v. CCK-8, we compared the effects of the i.v. administration of CRH antisera vs. normal rabbit serum on this parameter. IR-ACTH and IR-corticosterone responses to i.v. CCK-8 were significantly reduced in the context of pretreatment with CRH antisera compared to the administration of normal rabbit serum.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1991

Effects of short and long duration hypothyroidism and hyperthyroidism on the plasma adrenocorticotropin and corticosterone responses to ovine corticotropin-releasing hormone in rats.

We report here a study of the plasma ACTH and corticosterone responses to synthetic ovine CRH (oCRH) in hypothyroid and hyperthyroid rats studied 7, 15, and 60 days after either thyroidectomy or the administration of pharmacological doses of T4. The purpose of this study was to further clarify the time-dependent effects of alterations in thyroid status on the functional integrity of the hypothalamic-pituitary-adrenal axis and to aid in the interpretation of the oCRH stimulation test in hypo- and hyperthyroid states. Our data demonstrate that hypothyroid rats have a significant reduction in the cerebrospinal fluid (CSF) levels of corticosterone and a significant decrease in adrenal weight in association with significant increases in the plasma ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during the oCRH stimulation test was significantly reduced in hypothyroidism. With increasing duration of thyroidectomy-induced hypothyroidism, there was a progressive fall in CSF corticosterone levels, a progressive increase in the plasma ACTH response to oCRH, and a gradual normalization of the corticosterone responses to the ACTH released during oCRH stimulation. Our findings in hyperthyroid rats were generally the converse of those seen in hypothyroidism. Hence, there was a significant increase in the CSF levels of corticosterone and a significant increase in adrenal weight in association with an initial slight decrease in the ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during oCRH stimulation was significantly increased. There was a gradual increase in the magnitude of the rise in CSF corticosterone levels with time, as well as a gradual normalization of adrenocortical responses during oCRH stimulation. The ACTH plasma clearance rates were similar in hypo-, hyper-, and euthyroid rats. Our data do not permit definitive identification of the precise locus in the hypothalamic-pituitary-adrenal axis that is principally affected by experimentally induced alterations in thyroid status. However, these data are most compatible with a subtle hypothyroid-induced centrally mediated adrenal insufficiency and a subtle hyperthyroid-induced centrally mediated hypercortisolism. These data also suggest that alterations in hypothalamic-pituitary-adrenal function in states of disturbed thyroid function become somewhat more pronounced as the duration of thyroid dysfunction increases. The fact that pituitary-adrenal responses to oCRH are consistently altered in states of thyroid dysfunction may be relevant to the clinical interpretation of oCRH stimulation tests.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

Glucocorticoids inhibit estradiol-mediated uterine growth: possible role of the uterine estradiol receptor.

Stress-related activation of the hypothalamic-pituitary-adrenal axis (HPA) is associated with suppression of the reproductive axis. This effect has been explained by findings indicating that corticotropin-releasing hormone suppresses hypothalamic gonadotropin-releasing hormone (GnRH) secretion via an opioid peptide-mediated mechanism, and that glucocorticoids suppress both GnRH and gonadotropin secretion and inhibit testosterone and estradiol production by the testis and ovary, respectively. To evaluate whether glucocorticoids suppress the effects of estradiol on its target tissues, we examined the ability of dexamethasone to inhibit estradiol-stimulated uterine and thymic growth in ovariectomized rats. Estradiol alone, given daily for 5 days, caused dose-dependent uterine and thymic growth. Dexamethasone alone, given daily for 5 days, caused a dose-dependent decrease in body weight gain and in thymic growth. When estradiol and dexamethasone were administered simultaneously, however, body weight gain and thymic growth were also inhibited (p less than 0.05). Dexamethasone decreased estradiol-induced uterine cytosolic and nuclear estrogen receptor concentrations (E2 R0, p less than 0.05; E2nR0, respectively), but had no effect on estradiol-induced progesterone receptor concentrations (P4R0, p greater than 0.05). Levels of uterine glucocorticoid receptors were not affected by estrogen and/or dexamethasone treatment. These findings suggest that stress levels of glucocorticoids, administered over a 5-day interval, block the estradiol-stimulated growth of female sex hormone target tissues. This effect may be partially mediated by a glucocorticoid-induced decrease of the estradiol receptor concentration. Thus, another mechanism by which the HPA may influence reproductive function during stress is by a direct effect of glucocorticoids on the target tissues of sex steroids.

Animals↗
PubMed1990

Interactions between tumor necrosis factor-alpha, hypothalamic corticotropin-releasing hormone, and adrenocorticotropin secretion in the rat.

We studied the effects of tumor necrosis factor-alpha (TNF alpha), a macrophage-derived pleiotropic cytokine produced during the inflammatory/immune response, on the function of the hypothalamic-pituitary-adrenal (HPA) axis of the rat. Intravenous injections of TNF alpha stimulated plasma ACTH and corticosterone secretion in a dose-dependent fashion. This effect was inhibited by a rat CRH antiserum that was administered to the rats 1 h before the TNF alpha injections. This suggested that CRH is a major mediator of the HPA axis response to TNF alpha. We subsequently evaluated the ability of TNF alpha to influence CRH and ACTH secretion in vitro by explanted rat hypothalami in organ culture and by dispersed rat anterior pituicytes in primary culture respectively. Hypothalami were incubated for 40 min with graded concentrations of TNF alpha (10 pM to 1 microM). This cytokine stimulated CRH secretion in a dose-dependent fashion, with an EC50 of 6.7 x 10 pM (P less than 0.05). Preincubation of hypothalamic explants with dexamethasone, indomethacin (1 microM), eicosatetraynoic acid (10 microM), or nordihydroguaiaretic acid (30 microM) resulted in inhibition of TNF alpha-stimulated CRH secretion (P less than 0.05). Interestingly, 4-h incubation with TNF alpha had no effect on ACTH secretion from rat anterior pituicytes at a concentration of 10 nM. Higher concentrations of TNF alpha (100 nM and 1 microM), however, elicited a dose-dependent increase in the ACTH concentration in the medium. Our results suggest that TNF alpha represents one of the immune response mediators that directly or via stimulation of other cytokines act as activators of the HPA axis during immune/inflammatory reactions. This effect appears to be glucocorticoid suppressible and eicosanoid mediated. The primary site of action of TNF alpha appears to by the hypothalamic CRH-secreting neuron. Some pituitary and adrenal effects of TNF alpha, however, cannot be excluded.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1990

Recovery of the rat hypothalamic-pituitary-adrenal axis after discontinuation of prolonged treatment with the synthetic glucocorticoid agonist dexamethasone.

To evaluate the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after discontinuation of prolonged exposure to glucocorticoids, we employed adult male Sprague-Dawley rats which were implanted sc with osmotic minipumps filled with saline (vehicle) or dexamethasone (DEX), 100 micrograms/day, for 7 days. At the end of the glucocorticoid treatment period, the minipumps were removed and both saline- and DEX-treated rats were randomly assigned to five different groups tested at 1, 3, 7, 14, and 21 days after removal of the minipumps. Each group was divided into two subgroups receiving either arecoline (ARE), or ovine CRH (oCRH) stimulation tests. ARE was chosen because it has been shown to selectively stimulate the hypothalamic CRH neuron, whereas oCRH was selected as a probe of the pituitary component of the HPA axis. ARE (0.2 mg/kg) and oCRH (10 micrograms/kg) were injected iv to catheterized, freely moving rats and serial blood samples for plasma ACTH and corticosterone determinations were drawn from the catheter before, and 5, 15, 30, and 60 min after the injection. The day after the tests were performed, the rats were killed by decapitation, and body, adrenal and thymus weights, as well as hypothalamic CRH and pituitary ACTH content were determined. On the day of the stimulation tests, basal plasma levels of ACTH and corticosterone were not different between saline- and DEX-treated rats at any time-point after discontinuation of treatment. The ACTH response to ARE, on the other hand, was suppressed one day after, but became normal 3 days after discontinuation of DEX treatment. ACTH response to oCRH normalized later, after 7 days. Interestingly, corticosterone responses to both ARE and oCRH normalized 7 days after discontinuation of glucocorticoid administration. Body, adrenal and thymus weights were significantly reduced by DEX treatment. They recovered slowly and only after 22 days there was no difference between DEX- and saline-treated rats in body and adrenal weight. In contrast, thymus weight was still low on day 8, began to increase after 15 days, and by day 22 did not reach the values recorded in saline-treated rats. Hypothalamic immunoreactive CRH content was not different between DEX- and saline-treated rats, whereas the content of ACTH in the pituitary gland was lower in the DEX-treated rats the second day after discontinuation of GC treatment, normalized after 4 days and increased significantly after 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗