24-hour changes in ACTH, corticosterone, growth hormone, and leptin levels in young male rats subjected to calorie restriction

Calorie restriction of young male rats increases plasma prolactin, decreases luteinizing hormone (LH) and testosterone, and disrupts their 24 h secretory pattern. To study whether this could be the consequence of stress, we examined the 24 h variations of plasma adrenocorticotropic hormone (ACTH) corticosterone, growth hormone (GH), leptin, and adrenal corticosterone. Rats were submitted to a calorie restriction equivalent to a 66% of usual intake for 4 weeks, starting on day 35 of life. Controls were kept in individual cages and allowed to eat a normal calorie regimen. Significantly lower ACTH levels were detected in calorie-restricted rats. Plasma corticosterone levels during the light phase of the daily cycle were significantly higher in calorie-restricted rats. Time-of-day variation in plasma ACTH and corticosterone levels attained significance in calorie-restricted rats only, with a maximum toward the end of the resting phase. The daily pattern of adrenal gland corticosterone mirrored that of circulating corticosterone; however, calorie restriction reduced its levels. Plasma ACTH and corticosterone correlated significantly in controls only. Calorie restriction decreased plasma GH and leptin, and it distorted 24 h rhythmicity. In a second study, plasma ACTH and corticosterone levels were measured in group-caged rats, isolated control rats, and calorie-restricted rats during the light phase of the daily cycle. Plasma ACTH of calorie-restricted rats was lower, and plasma corticosterone was higher, compared with isolated or group-caged controls. The changes in the secretory pattern of hormones hereby reported may be part of the neuroendocrine and metabolic mechanisms evolved to maximize survival during periods of food shortage.     

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.     

Selenium deficiency impairs corticosterone and leptin responses to adrenocorticotropin in the rat

Selenium deficiency causes oxidative stress and impairs steroidogenesis in vitro. Leptin is closely related to the hypothalamo-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis at the central level while corticosteroids have been shown to stimulate leptin secretion in most studies. We hypothesized that oxidative stress impairs adrenal steroidogenesis and decreases leptin production in vivo. The goal of this study was to investigate in rats the effects of selenium deficiency and oxidative stress on adrenal function and on leptin concentrations. Weanling rats were fed a selenium-deficient (Se-) or selenium-sufficient (Se+) diet for 4-10 weeks. Selenium deficiency caused a marked decrease in liver (> or = 99%) and adrenal (> or = 81%) glutathione peroxidase (GPx) activities. Selenium deficiency did not affect basal and short-term adrenocorticotropin (ACTH) stimulated corticosterone or leptin concentrations. In contrast, after long-term ACTH stimulation, selenium deficiency caused a doubling in adrenal isoprostane content and blunted the increase in corticosterone and leptin concentrations observed in Se+ animals. Plasma leptin concentrations were 50% lower in Se- compared to Se+ animals following long-term ACTH. Our results suggest that oxidative stress causes a decrease in circulating corticosterone in response to ACTH, and, as a consequence, a decrease in plasma leptin concentrations.     

Periodic maternal deprivation and lesion of anterodorsal thalami nuclei induce alteration on hypophyso adrenal system activity in adult rats

The hypothalamic-pituitary-adrenal (HPA) axis is normally regulated by extrahypothalamic limbic structures, among these, the anterodorsal thalami nuclei (ADTN), which exert an inhibitory influence on HPA, in basal and acute stress conditions in rats. In the present work we have investigated whether neonatal maternal deprivation (MD) produces long-term changes in the ADTN regulation of HPA activity. Maternal deprivation, in female rats, for 4.5 hs daily, during the first 3 weeks of life, produced at 3 months old, a significant decrease in plasma ACTH concentration (p<0.001) and an increase in plasma corticosterone (C) (p<0.001), compared to control non-deprived rats (NMD). Also MD showed higher plasma epinephrine (E) and norepinephrine (NE) levels than NMD rats. The increase of NE (66.6% p<0.001) was higher than that observed in E (19%). After 30 days of ADTN lesion, plasma ACTH values were higher than in sham lesioned rats, in both NMD and MD animals. ACTH response was greater in MD rats. Plasma C, in NMD, was higher, whereas in MD lesioned animals, it was significantly lower than in sham lesioned. In MD rats, lesion produced a significant increase in plasma E and NE (p<0.001), and again, NE increase was higher than E increase. The more accentuated increase of NE than E, suggests sympathetic nervous system hyperactivity. In summary, neonatal maternal deprivation induces long-term alterations on HPA axis sensitivity and medullo adrenal secretion; enhanced sympathetic nervous system activity and, therefore affected the ADTN inhibitory influence on ACTH and adrenal glands secretion.     

Development of young rats and rabbits exposed to a strong electric field

Body growth and circulating levels of hormones were assessed in young rats and rabbits exposed to a 50-Hz electric field of 50 kV/m. Eight-week-old male rats were exposed 8 h/day for 4 weeks and rabbits were exposed 16 h/day from the last 2 weeks of gestation to 6 weeks after birth. The body and the organ growth of exposed rats were not statistically different from those of sham-exposed controls. No important differences from controls were observed in plasma levels of corticosterone, TSH, ACTH, and T4 or in adrenal levels of epinephrine, norepinephrine, and corticosterone although T3 was slightly, but significantly, decreased. No large histological changes in the thyroid or adrenals were noted. In rabbits, organ and body weights of exposed animals were comparable to those of controls. Plasma levels of various hormones (ACTH, GH, T3, T4, corticosterone, cortisol), serum glucose, triglycerides, and cholesterol were not significantly altered. Adrenal content of cortisol was lower, however, in exposed rabbits. No histological changes of the thyroid or adrenal glands were observed.     

Effect of the growth hormone-secreting tumor StW5 on pituitary and adrenal gland function in rats

A growth hormone-secreting tumor (StW5 was implanted into male rats and resulted in a tripling of adrenal weight concomitant with a 30% decrement in pituitary weight. Plasma concentrations of corticosterone in tumor-bearing (TB) rats were significantly elevated at rest or after ACTH injections or the stress of either anesthesia. The rise in plasma concentrations of corticosterone was due mainly to the large increment in adrenal size although a significant increase in adrenal responsiveness to ACTH was demonstrated in vitro. In addition, plasma corticosterone concentrations were higher in TB rats despite both a doubling of the blood volume and a 50% increase in liver capacity to metabolize corticosterone. Pituitary ACTH content was significantly lower in TB rats, but these pituitary glands could still release near-normal quantities of ACTH as shown both by in vitro incubations and adrenal corticosterone output following ether stress.     

Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.     

Effects of cortisol treatment on brain and adrenal corticotropin-releasing hormone (CRH) content and other parameters regulated by CRH

Corticotropin-releasing hormone (CRH) has been found in both hypothalamic and extrahypothalamic sites of the brain and also in the adrenal medulla. To study the timing and location of delayed glucocorticoid action in rats, we measured the effects of 2-day and 7-day cortisol treatment on immunoreactive CRH concentrations in hypothalamus, cerebral cortex, hippocampus, cerebellum, and adrenal gland. The activity of the hypothalamo-pituitary-adrenal (HPA) axis and the sympathoadrenal system were also measured. Studies were carried out both in the afternoon and/or in the morning, to get information about possible circadian changes. CRH contents were not changed in any brain areas studied, except there was a trend of decrease in the hypothalamus compared to vehicle in the afternoon due to the lack of circadian increase after 7-day cortisol treatment. Pituitary ACTH content decreased significantly after 7-day treatment, while beta-endorphin did not. Plasma levels of ACTH, corticosterone, norepinephrine and epinephrine and adrenal ACTH and beta-endorphin contents decreased after 2-day, adrenal CRH content after 7-day treatment with cortisol. Our findings suggest, that chronic cortisol treatment inhibits the circadian activation of the HPA axis at all levels but has variable effects on baseline measures because it causes different changes in release and synthesis at different sites.     

Angiotensin II stimulates the reactivity of the pituitary-adrenal axis in leptin-resistant Zucker rats, thereby influencing the glucose utilization

The HPA axis is hyperactive under conditions of leptin and insulin resistance as well as after ANG II administration. We hypothesized that a hyperreactivity of the HPA axis to ANG contributes to an impaired glucose utilization in obesity, since leptin resistance and an overactive renin-angiotensin-aldosterone system are features of obesity. Zucker rats were treated with ANG via subcutaneous minipumps (0, 0.9, and 9.0 mug/h; 4 wk). PA axis reactivity and glucose homeostasis were characterized after CRH treatment and during an oral glucose tolerance test (OGTT). The elevated plasma profile of corticosterone after CRH stimulation in saline-treated OZR compared with LZR confirmed that the sensitization of the PA axis depended on leptin resistance. Irrespective of the rat strain, circulating ANG levels and blood pressure were selectively increased after administration of 9 mug/h ANG (high ANG). Only high ANG induced an elevation of the corticosterone and glucose response after CRH stimulation in OZR but did not affect the ACTH secretion. During OGTT, corticosterone and consequently glucose increased in OZR after high ANG, whereas the insulin secretion was decreased. In the adrenal glands of OZR, AT(1A) receptor mRNA levels increased after high ANG. We conclude that the impairment of glucose utilization after ANG stimulation is potentiated in leptin-resistant rats as a result of a hyperreactive PA axis, thereby confirming the functional importance of a dysregulation within the HPA axis in metabolic syndrome or obesity. The ACTH-independent stimulation of corticosterone release and the selective increase of AT(1A) receptor mRNA in the adrenals of OZR indicated a sensitization of adrenals toward ANG, causing a stimulation of the PA axis.     

Sex differences in adrenocortical structure and function. XXVIII. ACTH and corticosterone in intact, gonadectomised and gonadal hormone replaced rats

Plasma ACTH and corticosterone (B) concentration, ACTH content in the anterior pituitary gland and B content in the adrenals were measured in intact, gonadectomised and testosterone or estradiol replaced rats. Plasma ACTH and B levels and adrenal B content were higher in female than male rats. Neither orchiectomy nor testosterone replacement had an effect on plasma ACTH and B concentration. Orchiectomy did not affect adrenal B content and decreased pituitary ACTH while testosterone significantly lowered ACTH and B content in studied glands. On the other hand ovariectomy did not change pituitary ACTH and adrenal B content and notably lowered concentrations of these hormones in the blood. Estradiol replacement resulted in an increase in plasma ACTH and B concentrations, an effect accompanied by a marked drop in pituitary ACTH and an increase in adrenal B. These findings indicate the distinct sex differences in basal plasma ACTH and B concentrations with higher values in female rats, an effect dependent on the stimulatory action of estradiol on pituitary-adrenocortical axis.     

Chronic leptin administration in developing rats reduces stress responsiveness partly through changes in maternal behavior

In adult rodents, leptin has been shown to significantly alter the activity of several neuroendocrine functions, including the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Leptin is generally believed to be inhibitory to HPA activity in adults. Developing rat pups have high circulating levels of leptin, which begs the question of leptin's physiological role in controlling basal and stress-induced adrenocortical activity in neonatal rats. In this study, we treated rat pups daily from days 2-9 (or 6-10) of life with either vehicle or leptin (1 or 3 mg/kg body wt, ip) and determined the effects on body weight gain, fat pad deposits, and HPA activity in 10-day-old pups. We measured hypothalamic CRF mRNA levels in vehicle- and leptin-treated pups by in situ hybridization and determined plasma ACTH, corticosterone, and leptin concentrations under basal conditions or following exposure to a 3-min ether stress. Because leptin activates sympathetic activity and energy expenditure in adults and possibly also in rat pups, and because litter temperature is an important determinant of maternal behavior, we also investigated whether chronic leptin administration would modify aspects of maternal care that are important for the maintenance of HPA function. Chronic leptin treatment increased circulating levels of leptin and had significant dose-related metabolic effects, including reduced body weight gain and fat pad weight in 10-day-old pups. Basal expression of CRF mRNA in the PVN or secretion of ACTH and corticosterone was not modified by leptin treatment. In contrast, chronically elevated leptin concentrations during the neonatal period significantly lowered CRF expression in the PVN 60 min after stress and reduced the duration of the ACTH response to stress in pups, suggesting that glucocorticoid feedback on the HPA axis might be altered by this treatment. In addition, mothers caring for pups injected with leptin displayed longer bouts of anogenital licking of pups than mothers of vehicle-treated rats. Given that this particular type of pup stimulation has been shown to influence stress responsiveness, it is possible that the maternal response modulates the effects of exogenous leptin treatment. In conclusion, our results demonstrate that the leptin signal is functional during the early developmental period and that leptin can modulate the hormonal response to stress in young rats either by a direct effect on the HPA axis or indirectly through changing some aspects of maternal behavior.     

Role of nitric oxide in the nicotine-induced pituitary-adrenocortical response.

Nitric oxide (NO) is a major signaling molecule and biological mediator of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the role of NO formed by endothelial (e), neuronal (n) and inducible (i) nitric oxide synthase (NOS) in the stimulatory effect of nicotine on the HPA axis in rats under basal conditions. Also possible interaction of NOS systems with endogenous prostaglandins (PG) in that stimulation was assessed. NOS and cyclooxygenase inhibitors were administered i.p. 15 min prior to nicotine (2, 5 mg/kg i.p.). Plasma ACTH and serum corticosterone levels were measured 1 h after nicotine injection. NOS blockers given alone did not markedly affect the resting ACTH and corticosterone levels. L-NAME (2-10 mg/kg), a broad spectrum NOS inhibitor considerably and dose dependently enhanced the nicotine-induced ACTH and corticosterone secretion. L-NNA (2 mg/kg) and 7-nitroindazole (7-NI 20 mg/kg), neuronal NOS inhibitors in vivo also significantly augmented the nicotine-induced ACTH and corticosterone levels. L-arginine greatly impaired the nicotine-induced hormone responses and reversed the L-NNA elicited enhancement of the nicotine-evoked ACTH and corticosterone response. In contrast to the constitutive eNOS and nNOS antagonists, an inducible NOS antagonist guanethidine (50-100 mg/kg i.p.) did not substantially affect the nicotine-elicited pituitary-adrenocortical responses. Indomethacin (2 mg/kg i.p.), a non-selective cyclooxygenase blocker abolished the L-NAME and L-NNA-induced enhancement of the nicotine-evoked ACTH and corticosterone response. These results indicate that NO is an inhibitory mediator in the HPA axis activity. Inhibition of its generation by eNOS and nNOS significantly enhances the nicotine-induced HPA response. Under basal conditions iNOS is not involved in the nicotine-induced ACTH and corticosterone secretion. Prostaglandins play an obligatory role in the response of HPA axis to systemic nicotine administration.     

Immunoneutralization of corticotropin-releasing hormone prevents the diurnal surge of ACTH

To determine whether CRH is required for the evening rise in plasma ACTH, rats were injected at 0800 hr with CRH antiserum (anti-CRH) or normal rabbit serum (NRS). Blood samples were taken through venous catheters at 0800 hr before treatment and at 1300, 1700, and 2100 hr. Plasma was assayed for immunoreactive ACTH and corticosterone. There was no significant difference in pretreatment values between the two groups. Immunoneutralization of CRH abolished the rise in plasma ACTH seen at 1700 hr in the NRS group but had little effect on earlier levels. The diurnal elevation in plasma corticosterone continued after anti-CRH treatment, but peak levels occurred earlier. Plasma ACTH and corticosterone were significantly correlated at the time of the diurnal surge, but not at 0800 hr or 1300 hr in the NRS controls or at any time point in the anti-CRH group. These results suggest that CRH is required for the diurnal surge of plasma ACTH. They also confirm previous observations by others that the adrenal cortex does not require active CRH or a diurnal surge of ACTH in order to exhibit a significant diurnal increase in secretion of corticosterone, and that factors other than CRH may be relatively more active than CRH in regulation of ACTH secretion during the time of circadian inactivity.     

Increased plasma corticosterone levels in bovine growth hormone (bGH) transgenic mice: Effects of ACTH,GH and IGF-I onin vitro adrenal corticosterone production

Previous work from our laboratory provided evidence for increased plasma corticosterone levels in mice transgenic for human and bovine growth hormone (GH). Corticosterone was elevated in both sexes, under both basal and ether-induced stress conditions. The objectives of the present study were to investigate thein vitro adrenal sensitivity to ACTH, GH and/or IGF-I in normal and bGH transgenic mice, to examine plasma corticosterone levels at different times of the day, and to determine plasma levels of ACTH in these animals. For the measurement of plasma corticosterone and ACTH levels, transgenic and normal siblings were housed 2 per cage and decapitated simultaneously within 20 seconds of the first disturbance of the cage. The corticosterone production byin vitro adrenal incubations did not differ between adrenals from normal and transgenic mice at the basal level or in the presence of different doses of ACTH. Growth hormone or IGF-I did not have any effect on corticosterone productionin vitro when given alone, and did not modify the effects of ACTH on the accumulation of corticosterone in the media. Plasma corticosterone concentrations were higher in transgenic than in normal animals in both morning and evening. Plasma concentrations of ACTH in animals killed in the morning were sharply increased in transgenic males as compared with their normal siblings. The results indicate that increased circulating levels of corticosterone in transgenic mice are not due to a potentiation of ACTH actions by GH or IGF-I, but rather to a chronic increase in plasma ACTH levels. The increase in ACTH is presumably a reflection of GH actions in the hypothalamic-pituitary system.     

Adult Consequences of Post-weaning High Fat Feeding on the Limbic–HPA Axis of Female Rats

The peripubertal period is critical for the final maturation of circuits controlling energy homeostasis and stress response. However, the consequence of juvenile fat consumption on adult physiology is not clear. This study analyzed the adult consequences of post-weaning fat feeding on limbic–hypothalamic–pituitary–adrenal (HPA) axis components and on metabolic regulators of female rats. Wistar rats were fed either a high fat (HF) diet or the normal chow from weaning to puberty or to 3 months of age. Additional groups crossed their diets at puberty onset. Plasma leptin, insulin, and corticosterone levels were determined by radioimmunoassay and their brain receptors by western blot analysis. Adult HF-fed animals though not overweight, had higher corticosterone and reduced glucocorticoid receptor levels in the hypothalamus and hippocampus, compared to the controls. The alterations in HPA axis emerged already at puberty onset. Leptin receptor levels in the hypothalamus were reduced only by continuous fat feeding from weaning to adulthood. The pre-pubertal period appeared more vulnerable to diet-induced alterations in adulthood than the post-pubertal one. Switching from fat diet to normal chow at puberty onset restored most of the diet-induced alterations in the HPA axis. The corticosteroid circuit rather than the leptin or insulin system appears as the principal target for the peripubertal fat diet-induced effects in adult female rats.     

Involvement of the corticoadrenal hormones in the pheromonal restoration of reproductive activity in aging rats

The involvement of the adrenal progesterone and corticosterone in the early gonadotropin secretion associated with the pheromonal restoration of ovarian cyclic activity (PRCA) in aging female rats is studied. PRCA is induced by male urinary pheromones and is preceded by an alpha-adrenergic-mediated release of the hypothalamic decapeptide luteinizing hormone-releasing hormone and plasma increases of estradiol, progesterone and the gonadotropins luteinizing hormone and follicle stimulating hormone. Aging reproductive Wistar female rats were used to study the effects of bilateral adrenalectomy and of a subcutaneous injection of the antisteroid RU486 on plasma levels of corticosterone, progesterone and gonadotropins in rats stimulated with nasal spraying of male urine (MU) or saline. The results demonstrate that progesterone and corticosterone released by MU are from adrenal origin, and that these adrenal secretory products are critical for MU-induced increase of gonadotropins. This suggests that olfactory stimulation of ACTH release stimulates adrenal release of progesterone and corticosterone, and both trigger the events that initiate the activation of the hypothalamus-pituitary-ovarian axis that leads to PRCA.     

Analysis of the mechanism of the stress-protective action of delta sleep-inducing peptide

By RIA there were studied the contents of corticosterone, ACTH, beta-endorphin and insulin in the blood plasma, met- and leu-enkephalin in different regions of the rat brain and in the adrenal glands after a 6-hour immobilization. The stress increased the content of corticosterone, ACTH, beta-endorphin, but not insulin in the blood plasma, and the levels of met-enkephalin in the adrenal glands, but decreased the met-enkephalin contents in the striatum. The injection of DSIP (0.1 mg/kg, i/p) blocked partly the elevation of corticosterone only. The authors propose, that stress-protective action of DSIP is realized with the involvements of the hypothalamo-pituitary-adrenal gland system.     

CRF-dependent and CRF-independent mechanisms involved in hypophysial-adrenal system activation by bacterial endotoxin.

The immune system and the hypothalamic-pituitary-adrenal (HPA) axis play important role in the overall inflammatory response. The mechanism through which lipopolysaccharide (LPS, endotoxin) stimulates the HPA axis is not well understood. In order to clarify the role of hypophysiotropic peptides of paraventricular origin in the effect of LPS on ACTH and corticosterone secretion, the effect of LPS was studied on rats with lesions of hypothalamic paraventricular nucleus (PVN). It was shown that 90 min after 2 mg/kg LPS i.p. the ACTH, but not the corticosterone response was effectively blunted in PVN-lesioned rats, as compared to sham operated animals. However, in PVN-lesioned rats 240 min after treatment with LPS a significantly higher plasma ACTH and corticosterone level was monitored. It is, therefore, suggested that in response to LPS activation of HPA both CRF(s)-dependent and CRF(s)-independent mechanisms are involved, even a direct effect of the adrenal cortex should be taken into account.     

Time-dependent mediators of HPA axis activation following live Escherichia coli

The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 × 10(7) CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE(2) was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE(2) correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 × 10(8) CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.     

Differential regulation of adrenal corticosteroids after restriction-induced drinking in rats

Water-restricted rats exhibit a rapid decrease in plasma corticosterone after drinking. The present study examined the effect of restriction-induced drinking on plasma aldosterone and plasma clearance of corticosterone. Rats were water restricted for 6-7 days and then killed before or 15 min after water administration; plasma and adrenal hormones were assayed. Plasma and adrenal corticosterone decreased after drinking without a change in plasma corticosteroid-binding globulin; plasma ACTH decreased or did not change. In contrast, plasma aldosterone did not change or increased after drinking; plasma renin activity was elevated by water restriction and increased further after drinking. In another experiment, rats were adrenalectomized, and corticosterone and aldosterone were replaced with pellets and osmotic minipumps, respectively. Rats were water restricted and killed. There was a small decrease in plasma corticosterone but no change in aldosterone after drinking in adrenalectomized animals. These data suggest that changes in plasma steroids after restriction-induced drinking result from zone-specific responses of the adrenal to known secretagogues, with minimal contribution from increased plasma clearance.