Circadian Corticosterone Rhythm Research Articles

Effects of suprachiasmatic transplants on circadian rhythms of neuroendocrine function in golden hamsters.

Grafts of fetal tissue including the suprachiasmatic nucleus (SCN) of the hypothalamus restore locomotor rhythmicity to behaviorally arrhythmic, SCN-lesioned Syrian hamsters. We sought to determine whether such transplants also reinstate endocrine rhythms in SCN-lesioned hamsters. In Exp 1, SCN lesions interrupted estrous cycles in a 14 h light, 10 h dark photoperiod and locomotor rhythms in constant dim red light (DD). SCN grafts that reinstated behavioral circadian rhythms consistently failed to reestablish estrous cycles. After ovariectomy, estradiol implants triggered LH surges at approximately circadian time 8 in 10 of 12 brain-intact control females and 0 of 9 SCN-lesioned, grafted females. Daily rhythms of the principal urinary melatonin metabolite, 6alpha-sulfatoxymelatonin, were not reestablished by behaviorally functional grafts. In Exp 2, SCN lesions eliminated locomotor rhythmicity in adult male hamsters maintained in DD. Seven to 12 weeks after restoration of locomotor activity rhythms by fetal grafts, hosts and sham-lesioned controls were decapitated at circadian times 4, 8, 12, 16, 20, or 24. Clear circadian rhythms of both serum corticosterone and cortisol were seen in sham-lesioned males, with peaks in late subjective day. No circadian rhythms in either adrenal hormone were evident in serum from lesioned-grafted males. Testicular regression, observed in intact and sham-lesioned males maintained in DD, was absent not only in arrhythmic SCN-lesioned hamsters given grafts of cerebral cortex, but also in animals in which hypothalamic grafts had reinstated locomotor rhythmicity. The pineal melatonin concentration rose sharply during the late subjective night in control hamsters, but not in SCN-lesioned animals bearing behaviorally effective transplants. Even though circadian rhythms of locomotor activity are restored by SCN transplants, circadian endocrine rhythms are not reestablished. Endocrine rhythms may require qualitatively different or more extensive SCN outputs than those established by fetal grafts.

The dorsomedial hypothalamic nucleus revisited: 1998 update.

This article reviews data that have accumulated since the early 1970s on the role of the dorsomedial hypothalamic nucleus (DMN) in neuroendocrine and autonomic homeostasis. Both the ventromedial hypothalamic nucleus (VMN) and the lateral hypothalamic area (LHA) project to the DMN, which in turn projects to the paraventricular nucleus of the hypothalamus (PVN), thus placing the DMN at an important nodal point of neuroendocrine/autonomic circuitries. The DMN is composed of cells and fibers containing neuropeptide Y (NPY), and the nutritional status (starvation-refeeding) is reflected in NPY levels of both VMN and DMN in Sprague-Dawley, Zucker (fa/fa), and corpulent rats (cp/cp JCR:LA). The DMN is involved in the final common pathway of corticotrophin-releasing hormone (CRH) secretion by the PVN, sympathetic nervous system outflow to the adrenal gland, and brown adipose tissue (BAT) thermogenesis. The DMN is also part of a "fear circuitry" regulating cardiovascular responses to stress such as myocardial blood flow and the tachycardia associated with the defense reaction. This appears to be mediated by a gamma amino butyric acid (GABA) mechanism. Although exhibiting reduced ponderal and linear growth and hypophagia and hypodipsia, the rat with DMN lesions (DMNL rat) has normal body composition, anabolic hormone levels, and intermediary metabolism, and it responds normally to numerous endocrine, nutritional, intra- and extracellular thirst and body weight-regulatory challenges. The DMNL rat shows normal efficiency of food utilization, but shows an attenuated response to the feeding-stimulatory effect of insulin. The only other lesion-induced abnormalities are hyperprolactinemia and a disrupted circadian corticosterone rhythm. The hyperprolactinemia in DMNL rats appears to be related to an attenuation of dopamine (DA). Rats with DMNL are capable of mating and can bear offspring, but there is a dramatic effect on litter size and other litter parameters that only improves when one parent is a DMNL rat. Antiaging effects produced by DMNL are evident in the prevention of age-associated microalbuminuria and kidney lesions, as well as, in prevention of the age-related decline in circulating insulin-like growth factor I (IGF-I). Recent evidence suggests that DMN, together with the VMN and the arcuate nucleus (ARC) of the hypothalamus, may be part of the circuitry that is responsive to the feedback signal from adipose tissue by the hormone leptin. The above findings and others suggest that the DMN plays a diverse role in physiological regulatory processes.

Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function.

Leptin is thought to regulate energy balance through effects on food intake and thermogenesis. In addition, leptin may serve as a mediator of the neuroendocrine response to starvation, and may modulate the stress response and the timing of puberty. A role for leptin in development is suggested by the presence of neuroendocrine and structural neuronal abnormalities in ob/ob mice with genetic leptin deficiency. Here, we sought to determine the ontogeny of leptin expression and its relationship to the developing neuroendocrine axis. Leptin increased 5-10-fold in female mice during the second postnatal week independent of fat mass, and declined after weaning. The rise in leptin preceded the establishment of adult levels of corticosterone, thyroxine, and estradiol. In contrast to adult mice, leptin was not acutely regulated by food deprivation during the early postnatal period. Circadian rhythms of leptin, corticosterone, and thyroxine were regulated by food intake in adult mice. When ad libitum feeding was restricted to the light cycle, peak corticosterone levels were shifted to the beginning of the light cycle and coincided with the nadir of leptin. The inverse relationship between leptin and corticosterone was maintained such that a rise in leptin after feeding was associated with a decline in corticosterone. To determine whether changes in corticosterone during food restriction are mediated by leptin, we compared the patterns of corticosterone levels among ob/ob, db/db, and lean mice. Despite their higher basal levels of corticosterone, leptin deficiency in ob/ ob mice did not prevent the nocturnal rise in corticosterone. In contrast, the nocturnal surge of corticosterone was blunted in db/db mice. Therefore, it is likely that factors in addition to leptin are involved in the regulation of the circadian rhythm of corticosterone. The temporal relationship between leptin and other hormones in neonatal and adult mice suggests that leptin is involved in the maturation and function of the neuroendocrine axis.

Ultradian rhythm of basal corticosterone release in the female rat: dynamic interaction with the response to acute stress.

The present study investigated the dynamic regulation of the hypothalamo-pituitary-adrenal axis and its significance to acute stress responsiveness in the female rat. An automated, frequent blood-sampling technique allowed the circadian rhythm of corticosterone to be resolved into a series of pulses. These were equally distributed (mean interval, 50.9 +/- 3.7 min) throughout the 24-h cycle, but their magnitude varied significantly, being higher between 1800-2200 h (137 +/- 9 ng/ml) than between 0600-1000 h (75 +/- 17 ng/ml). This pattern of release indicates continuous, but variable, activity of the axis throughout the day. The pulsatile ultradian rhythm suggested alternate periods of secretion and inhibition, which were found to have a profound effect on the corticosterone responses to acute stress. Noise stress (10 min, 114 decibels) evoked a transient increase in corticosterone, which reached a maximum (377 +/- 87 ng/ml) 20 min after onset. However, within this group (n = 26) the response varied depending on the underlying basal activity. When stress coincided with a rising (secretory) phase of a pulse, corticosterone concentrations rose to 602 +/- 150% of mean basal concentrations (P < 0.001). In contrast, when stress coincided with a falling (nonsecretory) phase of a pulse, a significantly smaller response, no greater than a basal pulse, was evoked. Thus, the alternate periods of secretion and inhibition generating basal hypothalamo-pituitary-adrenal activity are an important determinant of responses to acute stress.

Prenatal stress induces a phase advance of circadian corticosterone rhythm in adult rats which is prevented by postnatal stress

Prenatal and postnatal stressors can have different long-term neuroendocrine effects including modifications of stress-induced corticosterone secretion. However, very little is known about the possible long-term effects of prenatal or postnatal stress on the rhythmicity of basal corticosterone secretion in adult offspring. Corticosterone levels were thus determined at six different time points over 24 h in adult rats whose mothers had undergone restraint stress manipulations. The results demonstrate that prenatal stress induces a phase advance in the evening increase of corticosterone levels, and that this change is prevented by postnatal stress. It thus appears that the circadian system governing the HPA axis is modifiable by a prenatal stress, and remains susceptible to compensatory changes during the postnatal period.

Effects of the circadian rhythm of corticosteroids on leukocyte-endothelium interactions in the AM and PM

Circadian rhythms are responsible for a number of key cycles within the body. In vivo microscopy was used to investigate the hypothesis that the circadian rhythm of corticosterone in rats produces different leukocyte-endothelium interactions throughout the day. The data indicate that corticosterone levels range from 12 ng ml in the AM to 260 ng ml in the PM. In contrast, the number of circulating polymorphonuclear leukocytes (PMNs) yields peak values in the AM (630 PMNs/μl) and trough values in the PM (262 PMNs/μl). During surgical stress there is a significant increase in the number of circulating PMNs in the PM but little change in the AM. Furthermore, there is significantly greater leukocyte-endothelium adhesion in the PM (5.2 cells/100 μm) than in the AM (2.9 cells/100 μm). Addition of the chemoattractant FMLP increased adhesion 125% in the AM but only 62% in PM. Both exogenous glucocorticoid supplementation for 2 weeks and bilateral adrenalectomy abolished the circadian rhythms of circulating PMNs, the number of sticking white blood cells and the initial stages of an acute inflammatory response. These findings suggest that the circadian rhythm of corticosterone alters leukocyte-endothelium interactions throughout the day.

Effects of Bilateral Olfactory Bulbectomy on Circadian Rhythms of ACTH, Corticosterone, Motor Activity and Body Temperature in Male Rats

Bilateral olfactory bulbectomy (BOX) has major biochemical and behavioral effects, and is one of the most widely investigated of animal models of depression. We studied the consequences of BOX in male rats, on the organization of endogenous circadian rhythms for ACTH, corticosterone (Cort), motor activity (MA) and body temperature (BT). Mean levels were increased for Cort and MA, whereas no significant changes were observed for ACTH and BT. Significantly higher plasma Cort morning values were evidenced in BOX than sham-operated animals. In addition, compared with the single prominent power spectrum for the 24 hours period of control rats, the BOX animals displayed substantially lower 24 hours spectral power for the MA and BT circadian rhythms. These alterations suggest that olfactory bulbectomy, by disruption of the afferences and efferences, induced drastic changes in the function of the endogenous clock or of its regulating systems. From this point of view, bulbectomized rats may therefore be a valuable model to studying the etiology of psychiatric disorders with rhythm disturbance.

Adaptation of circadian corticosterone and catecholamine rhythms to light-dark cycle reversal in the rat.

Circadian rhythms of urinary excretion of corticosterone and catecholamines were examined in the rat before and after phase reversal of a 12-hour light and 12-hour dark cycle. After the reversal, the acrophase of rhythm was delayed and became constant again on the 6th day for corticosterone and on the 7th or 8th day for adrenaline. The ratios of light-period output to 24-hour output of adrenaline and noradrenaline, however, adjusted to the new light-dark cycle on 10th day, whereas this ratio became constant on 6th day for corticosterone. Thus, circadian corticosterone rhythm seems to adapt to light-dark reversal more quickly than catecholamine rhythm.

Alteration in circadian rhythm of plasma corticosterone in rats following sociopsychological stress induced by communication box

The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychological stressed experimental group. The stress exposure was loaded for 1 h between 0900 and 1000, daily. The changes in circadian rhythm of plasma corticosterone were studied following the 3-day, 5-day, or 10-day stress exposure, respectively. Plasma corticosterone levels of foot shocked rats and nonfoot shocked rats following the 3-day or 5-day stress exposure were significantly higher than those of control rats. Particularly, the marked elevation of plasma corticosterone was observed at the peak time of circadian rhythm (2100) in the both stress groups. Consequently, the amplitude of 24 h rhythm increased significantly, but the acrophase was not changed. However, the changes of plasma corticosterone levels of both stress groups following the 10-day stress exposure approached those of control group. These results suggest that the repeated exposure of sociopsychological stress can influence the circadian rhythm of plasma corticosterone. The communication box method may be a valuable tool for researching the etiology of human psychiatric disorders with rhythm disturbance.

Analysis of corticosterone in rat plasma by high-performance liquid chromatography

A sensitive and specific high-performance liquid chromatographic assay for the determination of corticosterone in rat plasma using dexamethasone as the internal standard is reported. Rat plasma (0.5 ml) is extracted with methylene chloride, washed with 0.1 M sodium hydroxide and then with water. The extract is analyzed by HPLC on a C 18 column with ultraviolet absorbance detection at 254 nm. Pooled rat plasma was treated with activated decolorizing carbon to remove endogenous corticosterone, and was then used to prepare standards for the assay. Using 0.5 ml plasma for extraction, the detection limit of the assay is 10 ng/ml. The standard curve is linear over the concentration range 10–500 ng/ml. The recovery of corticosterone after extraction was independent of concentration and ranged from 87 to 95%. The coefficient of variation for intra-day and inter-day precision ranged from 2.4 to 7.4% and 2.1 to 8.7%, respectively. In addition, for concentrations ranging from 10 to 500 ng/ml the accuracy is within 5% of the spiked standards. The assay was utilized to examine the circadian rhythm of plasma corticosterone, and to examine the effect of immobilization stress on corticosterone levels in rats.

Resynchronisation of the circadian corticosterone rhythm after a LD‐shift in juvenile and adult mice

Resynchronisation of the circadian corticosterone rhythm after a LD‐shift in juvenile and adult mice

Resynchronization of the circadian corticosterone rhythm after a light/dark shift in juvenile and adult mice.

Most of the extensive literature concerning the resynchronization of circadian rhythms after a Zeitgeber shift is devoted to the dependence of resynchronization on the mode of the shift and the strength of the Zeitgeber, as well as on the circadian function investigated. Ontogenetic influences have rarely been investigated. Therefore, we studied the resynchronization of several circadian rhythms in juvenile and adult female laboratory mice. We present here the results concerning the corticosterone rhythm. The daily rhythms were determined as transverse profiles (2-h intervals) before as well as 3, 7, and 14 days after an 8-h phase delay of the light/dark cycle produced by a single prolongation of dark time. The corticosterone concentration in serum was determined radioimmunologically. In the control animals the daily patterns were bimodal, with main maxima at the end of the light time and secondary ones just after lights on. Ontogenetic differences were small. In adult mice the amplitude was slightly increased due to an increase in the maximum values, and the time of highest hormone concentrations was slightly phase advanced. In juvenile mice, a distinct daily pattern with a phase position in relation to the light/dark cycle corresponding to that of control animals was present on the 3rd day after the Zeitgeber shift. The daily mean as well as the minimum and maximum values increased initially and reached the values of control animals during the second week. In adult animals, a pronounced daily rhythm with the normal phase position was present only at the 7th postshift day. The amplitude, daily mean, and maximum values were decreased, and the minimum values were increased. The initial values were not reached even after 2 weeks. The results show that resynchronization was faster in juvenile mice compared with adult mice. As a possible cause for the observed age-related differences, a not yet stabilized phase-coupling between various circadian rhythms is supposed.

Counterregulatory hormone responses during graded hyperinsulinermic euglycemia in conscious rats

It has been suggested that hyperinsulinemia per se may affect the levels of some counterregulatory hormones in the absence of hypoglycemia. We studied the effect of graded hyperinsulinemia and concomitant increased glucose metabolism on the levels of counterregulatory hormones by means of the 5-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3- 3H]-glucose infusion, in conscious rats. Insulin infusion rates (IIR) of 0, 0.5, 1, 3, and 16 mU/min, resulted in steady-state plasma insulin levels (mean ± SEM of 24±4, 44±3, 98±8, 418±48, and 6626±361 μU/ml, peripheral glucose uptake (PGU) of 3.1±0.2, 3.6±0.3, 5.4±0.3, 9.2±0.4, and 12.4±0.2 mg/min and hepatic glucose production (HGP) of 3.1±0.2, 2.4±0.4, 0.8±0.3, −0.1±0.2, and −0.5±0.3 mg/min, respectively. Plasma glucagon levels were half maximally suppressed between IIRs of 0.5 and 1 mU/min and maximally suppressed at 3 mU/min. The suppression exactly paralieled the inhibition of HGP ( r=0.87±0.04, p<0.02) but not the stimulation of PGU ( r=−0.66±0.12, p=NS). This suggests that the inhibition of HGP by insulin is at least partially mediated by a simultaneous suppression of plasma glucagon levels. The adrenal hormones corticosterone and epinephrine were not influenced during the clamp. Moreover, the circadian rhythm of corticosterone seemed unaffected. Plasma norepinephrine levels were increased (±50%, p<0.05) at IIRs of 1 mU/min and higher, suggesting an insulin-induced stimulation of the sympathetic nervous system when peripheral plasma insulin levels exceed 98±8 μU/ml. In conclusion, measurement of in vivo insulin action by means of the euglycemic clamp induces dose-dependent changes in the levels of glucagon and norepinephrine but not in epinephrine and corticosterone. This has to be taken into account because it is, in fact, the interaction between insulin and these counterregulatory hormones that determines the ultimate action of insulin on glucose metabolism in vivo.

The lateral hypothalamic area revisited: Neuroanatomy, body weight regulation, neuroendocrinology and metabolism

This article reviews findings that have accumulated since the original description of the syndrome that follows destruction of the lateral hypothalamic area (LHA). These data comprise the areas of neuroanatomy, body weight regulation, neuroendocrinology, neurochemistry, and intermediary metabolism. Neurons in the LHA are the largest in the hypothalamus, and are topographically well organized. The LHA belongs to the parasympathetic area of the hypothalamus, and connects with all major parts of the brain and the major hypothalamic nuclei. Rats with LHA lesions regulate their body weight set point in a primary manner and not because of destruction of a "feeding center". The lower body weight is not due to finickiness. In the early stages of the syndrome, catabolism and running activity are enhanced, and so is the activity of the sympathetic nervous system (SNS) as shown by increased norepinephrine excretion that normalizes one mo later. The LHA plays a role in the feedback control of body weight regulation different from ventromedial (VMN) and dorsomedial (DMN). Tissue preparations from the LHA promote glucose utilization and insulin release. Although it does not belong to the classical hypothysiotropic area of the hypothalamus, the LHA does affect neuroendocrine secretions. No plasma data on growth hormone are available following electrolytic lesions LHA but electrical stimulation fails to elicit GH secretion. Nevertheless, antiserum raised against the 1-37 fragment of human GHRF stains numerous perikarya in the dorsolateral LHA. The plasma circadian corticosterone rhythm is disrupted in LHA lesioned rats, but this is unlikely due to destruction of intrinsic oscillators. Stimulation studies show a profound role of the LHA in glucose metabolism (glycolysis, glycogenesis, gluconeogenesis), this mechanism being cholinergic. Its role in lipolysis appears not to be critical. In general, stimulation of the VMN elicits opposite effects. Lesion studies in rats show altered in vitro glucose carbon incorporation into several tissue fractions both a few days, and one mo after lesion production. Several of these changes may be due to the reduced food intake, others appear to be due to a "true" lesion effect.

Circadian rhythms of plasma corticosterone at different times after induction of diabetes. Responses to corticoadrenal stimulation in light and dark phases

In this study we have tried to determine the effects of streptozotocin-induced (50 mg/kg) diabetes (15 and 30 day duration) on circadian rhythms of plasma corticosterone concentrations and on the responsiveness of the adrenal glands to exogenously administered ACTH at the time of maximum and minimum levels of plasma corticosterone. Rats were kept under controlled lighting 12h light/12h dark (12L/12D) and fed ad libitum. The corticosteroid circadian pattern in control (C) rats is characterized as one in which peak corticosterone concentrations occur at the beginning of the dark phase (activity period), with a decrease over the remainder of the 24h period. Circadian rhythmicity of plasma corticosterone concentration was absent in the diabetic rats 15 days after induction (D15 rats), with higher mean levels than the C. However, in the diabetic rats 30 days after induction (D30 rats) there is a recovery of this rhythm with similar acrophase and amplitude to the C rats. One hour after stimulation by ACTH (5 IU/kg) at the time of maximum and minimum levels of plasma corticosterone, the C rats showed similar plasma corticosterone levels. In the D15 rats, levels of corticosterone in the light phase one hour after ACTH administration were higher than in the dark phase; being lower than C in this phase. The loss of capacity to respond during the dark phase may be due to adrenal blunting in this phase with high levels of plasma corticosterone. In D30 rats, there is a more noticeable loss of capacity for adrenal response in the light than in the dark phase, with values lower than C and D15 rats in both phases. These findings suggest that the duration of diabetes has a significant role in both plasma corticosterone rhythms and adrenal sensitivity to ACTH administration.

Glucocorticoids in the nonobese diabetic (NOD) mouse: Basal serum levels, effect of endocrine manipulation and immobilization stress

The NOD mouse is a recognized model for studying immunologically mediated insulin-dependent diabetes mellitus (IDDM). In most colonies, the disease appears with a greater preponderance in females than in males and castration alters the expression of the disease. The prevalence of diabetes may also vary depending upon environmental factors such as stress. Therefore, we measured in the NOD mouse serum glucocorticoid concentrations in basal and stress conditions. We observed in NOD as well as in C57BL/6 mice, taken as controls, a circadian rhythm of corticosterone, with females having higher values than males. After a single restraint stress, female and male NOD mice exhibit a comparable response, whereas after repeated stress, males respond significantly less than females, suggesting an adaptation phenomenon. In contrast, there is no difference in the pattern of corticosterone response of C57BL/6 females and males to both types of stress, but females always respond better than males. Moreover, whatever the stress considered, NOD mice generally exhibit a higher corticosterone response than C57BL/6 mice. The sexual dimorphism in diabetes expression in NOD mice may be related to the levels of corticosterone, a hyperglycemic hormone, in both basal and stress conditions. However, the understanding of corticosteroid effects in this model of type I IDDM is rather complex given their well known anti-inflammatory and immunosuppressive effects in other models of autoimmune diseases.

Circadian rhythms of corticosterone and catecholamine excretion in the rat after stress exposure

Circadian rhythms of corticosterone and catecholamine excretion in the rat after stress exposure

Sex and strain differences in the circadian rhythm fluctuation of endocrine and immune function in the rat: implications for rodent models of autoimmune disease

This study compares 24-h basal patterns of corticosterone and immunoreactivity for Lewis and Fischer (F344) strain rats. Significant differences in the circadian rhythm of plasma corticosterone were found across sex and strain. Male Lewis rats exhibited significantly lower 24-h corticosterone levels relative to female Lewis and male F344 rats. In addition, male Lewis rats were found to have higher mononuclear cell counts than female Lewis or male F344 rats, particularly in the peripheral blood and spleen compartments. Levels of CD4-bearing lymphocytes in blood, lymph node, and spleen were found to be higher in Lewis rats compared to the F344 strain over a 24-h period. In general, percentages of CD8- and major histocompatibility complex (MHC) class II-bearing lymphocytes were shown to vary over 24 h in all compartments across strains. Given that the Lewis rat has low basal levels of circulating corticosterone, and comparatively higher numbers of CD4-bearing lymphocytes, these factors may play a causative role in the known susceptibility of this strain to many experimental models of autoimmune disease.

Restoration of Circadian Corticosterone Rhythm in Ventromedial Hypothalamic Lesioned Rats

The effects of ventromedial hypothalamic (VMH) lesions on the circadian periodicity of blood corticosterone were studied in female rats. The rats were kept on a 12-hour light/12-hour dark illumination regimen and fed ad libitum. Three, 10 and 12 weeks after the VMH lesions, the concentrations of blood corticosterone were measured every 4 h for 48 h in the same unanesthetized rats. Three weeks after the operation, the circadian rhythm in VMH-lesioned rats was disturbed and disappeared. The corticosterone levels at 03:00, 07:00, and 11:00 were significantly higher than those in sham-operated rats. 10 and 12 weeks after the operation, the circadian rhythm, however, was notable (p less than 0.05, p less than 0.05). The elevated mean corticosterone levels over 48 h at 3 weeks after the operation decreased at 10 and 12 weeks. The sham-operated rats showed a significant circadian rhythm at 3, 10 and 12 weeks after the operation (p less than 0.001 in each period) with a peak concentration at 19:00 and through at 07:00. These findings show that the corticosterone circadian rhythms which were disturbed in the dynamic phase after VMH lesions recovered in the static phase of obesity, suggesting that the ventromedial hypothalamus is not an essential biological clock of circadian corticosterone rhythm.

Alterations in the binding characteristics of glucocorticoid receptors from obese zucker rats

Obese Zucker rats appear to lack a circadian rhythm of serum corticosterone and maintain relatively high concentrations throughout the 24-h day. The binding characteristics of glucocorticoid receptors in lean and obese Zucker rats were examined in three tissues suggested to be involved in the feedback inhibition of corticosterone: the anterior pituitary, hypothalamus and hippocampus. Hepatic glucocorticoid receptors were also examined to determine if receptor alterations exist in a peripheral tissue. The dissociation constant (Kd) of glucocorticoid receptors in the anterior pituitary of obese rats was 50% greater than the Kd of receptors derived from lean rats. This suggests a decrease in the affinity of these receptors and could indicate a reduced feedback inhibition of corticosterone at the anterior pituitary. Hepatic glucocorticoid receptors of obese rats also showed an increase (150%) in the Kd of binding and a reduction (40%) in the number of receptors. No difference was observed in the Kd or maximal binding of receptors from the hypothalamus or hippocampus of lean and obese rats. It appears that glucocorticoid receptor alterations exist in obese Zucker rats and that these alterations may affect the drive of the pituitary-adrenal axis and possibly the expression of obesity.