Biomedical subjects

G Croiset

Publications and source records attributed to G Croiset.

At least 19 recordsLinked to original sources

PubMed2001

Long-term sensitization of cardiovascular stress responses after a single stressful experience.

There is evidence that the experience of traumatic events may play a role in the pathogenesis of somatic diseases, including cardiovascular disorders. In this study, telemetry was used to investigate the long-term effects of a single stressful experience on cardiovascular and behavioral responses to novel challenges 2 weeks later. Rats were exposed to footshocks and tested for sensitization using the following challenges: novel cylinder (Day 14); shock prod acquisition test (Day 15); and shock prod retention test (Day 16). No difference in basal somatomotor activity (SA), heart rate (HR) and blood pressure between preshocked rats and control rats was found. However, preshocked rats displayed an enhanced blood pressure response compared to controls during the shock prod acquisition test and the shock prod retention test. No differential increase in HR response between both groups was found. During the novel cylinder test, the preshocked rats displayed less SA while no behavioral differences were found in the shock prod acquisition test and the shock prod retention test. We conclude that a single stressful experience induces long-term sensitization of blood pressure responses to novel challenges that are not necessarily linked to sensitized behavioral responses. The footshock model may be a useful model to study autonomic hyperresponsivity found in posttraumatic stress disorder (PTSD).

Animals↗

PubMed2001

CRH signalling in the bed nucleus of the stria terminalis is involved in stress-induced cardiac vagal activation in conscious rats.

The bed nucleus of the stria terminalis (BNST) is involved in autonomic and behavioral reactions to fearful stimuli and contains corticotropin-releasing hormone (CRH) fibers and terminals. The role of CRH in the medial part of the BNST in the regulation of heart rate (HR) and PQ interval of the electrocardiogram was studied under resting conditions and conditioned fear stress in freely moving rats. Microinfusion of CRH (0.2 microg/0.6 microl) in the medial BNST under resting conditions significantly enhanced HR as compared to saline treatment, but did not reduce the PQ interval, indicating that exogenous CRH in the medial BNST can activate both the sympathetic and parasympathetic cardiac outflow. In addition, CRH induced a slight increase in gross locomotor activity, an effect that succeeded the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but likely a direct effect of CRH. CF was induced by 10-min forced exposure to a cage in which the rat had experienced footshocks (5 x 0.5 mA x 3s) the day before. alpha-helical CRH(9-41) (alphahCRH; 5 microg/0.6 microl), a non-selective CRH receptor antagonist, or saline was infused into the medial BNST of rats prior to CF. CF induced freezing behavior, associated with an increase in HR and PQ interval, indicating activation of sympathetic and vagal outflow to the heart. alphahCRH significantly reduced the PQ response, but enhanced the tachycardia, suggesting inhibition of vagal activity. In addition, alpha-helical CRH(9-41) reduced the freezing response. Taken together, the data provide first evidence that CRH, released in the medial BNST during stress, contributes to cardiac stress responses, particularly by activating vagal outflow.

Animals↗

PubMed2000

Role of corticotropin-releasing factor, vasopressin and the autonomic nervous system in learning and memory.

Learning and memory are essential requirements for every living organism in order to cope with environmental demands, which enables it to adapt to changes in the conditions of life. Research on the effects of hormones on memory has focused on hormones such as adrenocorticotropic hormone (ACTH), glucocorticoids, vasopressin, oxytocin, epinephrine, corticotropin-releasing factor (CRF) that are released into the blood and brain following arousing or stressful experiences. Most of the information have been derived from studies on conditioned behavior, in particular, avoidance behavior in rats. In these tasks, an aversive situation was used as a stimulus for learning. Aversive stimuli are associated with the release of stress hormones and neuropeptides. Many factors play a role in different aspects of learning and memory processes. Neuropeptides not only affect attention, motivation, concentration and arousal or vigilance, but also anxiety and fear. In this way, they participate in learning and memory processes. Furthermore, neuropeptides such as CRF and vasopressin modulate the release of stress hormones such as epinephrine. In turn, systemic catecholamines enhance memory consolidation. CRF and vasopressin are colocalized in neurons from the nucleus paraventricularis, which project to nuclei in the brainstem involved in autonomic regulation. The objective of this paper is to discuss the role of CRF, vasopressin, and the autonomic nervous system (ANS) in learning and memory processes. Both CRF and vasopressin have effects in the same direction on behavior, learning and memory processes and stress responses (release of catecholamines and ACTH). These neuropeptides may act synergistically or in a concerted action aimed to learn to adapt to environmental demands.

Animals↗

PubMed2000

Endogenous corticotropin-releasing hormone inhibits conditioned-fear-induced vagal activation in the rat.

The role of the endogenous corticotropin-releasing hormone (CRH) system in the regulation of heart rate, PQ interval (a measure of vagal activity), gross activity and release of adrenocorticotropic hormone (ACTH), noradrenaline and adrenaline into the blood during conditioned fear was studied in freely moving rats. Intracerebroventricular (i.c.v.) infusion of alpha-helical CRH-(9-41) (10 microgram/3 microliter), a non-selective CRH receptor antagonist, under resting conditions had no significant effect on gross activity, heart rate and PQ interval, indicating that alpha-helical CRH at this dose was devoid of agonist effects. Conditioned fear was induced by 10 min forced exposure to a cage in which the rat had experienced footshocks (5x0.5 mAx3 s) 1 day before. Conditioned-fear rats showed freezing behaviour, associated with an increase in heart rate, PQ interval, noradrenaline and adrenaline, indicating that the conditioned-fear-induced cardiac effects were the result of coactivation of the sympathetic and parasympathetic nervous system. The i.c.v. pre-treatment of rats with alpha-helical CRH significantly reduced the conditioned-fear-induced tachycardiac and ACTH response, and enhanced the increase in PQ interval, without affecting the noradrenaline and adrenaline response. These results suggest that endogenous CRH reduces the vagal response to conditioned-fear stress in rats. To test this, rats were pre-treated with atropine methyl nitrate (0.3 mg/kg, subcutaneously; s.c.), a peripherally acting cholinergic receptor antagonist. This resulted in a complete blockade of the alpha-helical CRH-induced decrease in heart rate response and increase in PQ interval. From these findings, it is concluded that endogenous CRH in the brain inhibits vagal outflow induced by emotional stress.

Adrenocorticotropic Hormone↗

PubMed2000

The role of the CRH type 1 receptor in autonomic responses to corticotropin- releasing hormone in the rat.

The involvement of the corticotropin-releasing hormone (CRH) type 1 receptor in CRH-induced cardiac responses was studied in freely moving rats. Intracerebroventricular (icv) infusion of 2 microg CRH under resting conditions resulted in a significant increase in heart rate (HR), but did not significantly affect the PQ interval of the electrocardiogram. This effect involves sympathetic nervous system (SNS) activation, since CRH-treatment resulted in a marked increase in plasma norepinephrine (NE) and epinephrine (E), and sympathetic blockade by subcutaneously injected atenolol (1 mg/kg), a beta1-selective adrenergic antagonist, completely prevented the CRH-induced tachycardia. CRH infusion after sympathetic blockade resulted in an elongation of the PQ interval, indicating CRH-induced vagal activation. Gross locomotor activity (GA) was determined to study its possible indirect effects on cardiac activity. Although CRH induced a marked increase in GA, this effect followed the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but was a direct effect of icv CRH. Treatment with CP-154,526 (icv, 10 or 25 microg), a selective CRH type 1 receptor antagonist, did not affect baseline HR, plasma NE and E, whereas it partially blocked the CRH-induced increase in HR, plasma NE and E levels. CP-154,526 treatment had no significant effects on baseline or CRH-induced changes in GA. These results indicate that CRH activates the sympathetic nervous system at least in part via the CRH type 1 receptor.

Adrenergic beta-Antagonists↗

PubMed1999

Long-term sensitization of Fos-responsivity in the rat central nervous system after a single stressful experience.

There is considerable evidence for a role of stressful experiences in psychosomatic disorders in humans, but the mechanisms leading to altered responsivity and the relative contributions of central and peripheral neuronal changes, however, are still under debate. To investigate the contribution of specific brain areas to sensitized responsivity, rats were exposed to a single brief session of inescapable footshocks (preshocked) or no shocks (control) in a gridcage. Two weeks later, an electrified prod was inserted in the home cage for 15 min and the behaviour recorded. One hour later rats were perfused and brain sections were stained for Fos protein immunoreactivity. The number of Fos positive neurons was quantified in 27 brain areas. No significant difference in behaviour was found between the groups during the shock prod challenge. A significantly higher number of Fos positive neurons was found in preshocked rats compared to controls in the following brain areas: agranular insular cortex, frontal cortex, nucleus accumbens, bed nucleus of the stria terminalis, basolateral amygdala, CA1 area of the hippocampus, paraventricular hypothalamic nucleus, dorsolateral central grey, locus coeruleus, nucleus of the solitary tract and lateral paragigantocellular nucleus. We conclude that altered reactivity to stressful challenges in brain areas involved in neuroendocrine and autonomic control may play a role in long-term sensitization of neuroendocrine and autonomic responses in preshocked rats under conditions where behavioural sensitization is not expressed.

Animals↗

PubMed1999

Sex differences in long-term stress-induced colonic, behavioural and hormonal disturbances.

Functional bowel disorders are more prevalent in women than in men, but the reason for this is unclear. Stressful experiences can increase the risk for or precipitate intestinal dysfunction. Using a model for long-term stress-induced sensitisation in rats, it was investigated whether male and female rats differ in susceptibility for long-term colonic, behavioural and hormonal disturbances following brief but intense stress. Male and female Wistar rats were fitted with chronic electrodes on proximal colon and given either a 15-minute session of foot shocks or no shocks. Two weeks later, rats were exposed to two different novel stressful challenges in the home cage: an electrified prod (day 14) and an 85 dB noise stressor (day 15). Digitalised colonic myoelectric spike burst activity was quantified automatically. Behaviour during prod and noise exposure was scored blindly from videotape. Resting plasma hormone concentrations at the end of the study were determined by radio-immuno assay. Following prod stress on day 14, both male and female preshocked rats showed a greater increase in colonic spike burst frequency than controls, but similar behaviour, and the dynamics of colonic motility differed between sexes. Following noise stress on day 15, only a small change in burst frequency was seen in all rats, but preshocked rats showed less self-grooming behaviour and there was a tendency for preshocked females to show increased noise-induced immobility. Preshocked rats also had lower levels of plasma free thyroxine. While both male and female rats show long-term stress-induced colonic sensitisation and hormonal changes, females show a different activation pattern of colonic motility, and may be more vulnerable for altered behavioural reactivity, following stress.

Adrenocorticotropic Hormone↗

PubMed1998

Conditioned fear-induced tachycardia in the rat: vagal involvement.

The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be used as a measure of vagal activity. Conditioned fear was induced by 10-min forced exposure to a cage in which the rat had previously experienced footshocks (5 x 0.5 mA x 3 s). In non-shocked controls, an increase in gross activity was found and a pronounced tachycardia, without changes in PQ interval. Conditioned fear rats showed immobility behaviour, associated with a less pronounced tachycardia and an increase in PQ interval. Noradrenaline was similarly increased in both groups, whereas adrenaline was increased in conditioned fear rats only. To further evaluate the role of the vagus, rats were exposed to conditioned fear after pre-treatment with atropine methyl nitrate (0.5 mg/kg, s.c.). Again, immobility was observed with a concomitant tachycardia, but without an increase in PQ interval. These results indicate that the autonomic nervous system is differentially involved in heart rate regulation in conditioned fear rats and in non-shocked controls: in non-shocked controls a predominant sympathetic nervous system activation results in an increase in heart rate, whereas in conditioned fear rats the tachycardiac response is attenuated by a simultaneous activation of sympathetic nervous system and parasympathetic nervous system.

Animals↗

PubMed1998

Vagal activation in novelty-induced tachycardia during the light phase in the rat.

The effects of repeated exposure to a novel test box on cardiac and behavioral activities (locomotion, rearing, grooming, scanning, and immobility) were studied in rats tested during the dark phase ("dark" rats) or the light phase ("light" rats) of the lighting cycle, using a telemetry system for registration of ECGs during the first and fifth tests. Heart rate (HR) was used to monitor sympathetic and parasympathetic activity; the PQ interval was used to monitor parasympathetic activity. Behavior was videotaped simultaneously. In light rats, the first and fifth exposures to the test box resulted in higher increases of active behavior and HR than in dark rats, whereas the duration of the PQ interval of the ECG was increased in light rats only. This indicates that in the light phase novelty induces active behavior associated with an increase in both sympathetic and vagal outflow, whereas in the dark phase behavioral activation is predominantly associated with increased sympathetic activity, without appreciable changes in vagal outflow. In addition, light rats showed less active behavior during the fifth than during the first exposure, indicating behavioral habituation. This behavioral habituation to the test box in the light phase coincided with vagal habituation (a diminution of the PQ interval). The increase of the tachycardiac response during the fifth exposure as compared to the first exposure suggests that it is not likely that sympathetic outflow was part of the habituation process. In dark rats no behavioral or cardiac habituation was found.

Animals↗

PubMed1998

The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal-axis and the induction of excessive grooming.

1. In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH1-24 (1 microg) induced a display of excessive grooming, and increased the plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation was blocked by pretreatment with dexamethasone, indicating that the effect of the (i.c.v.) injected peptide was not caused by a peripheral effect on the adrenal cortex. 2. Doses of 1 and 3 microg of a non-selective melanocortin-3/4-receptor antagonist (SHU 9119), or of 5 and 10 microg of a selective melanocortin-4-receptor antagonist ([D-Arg8]ACTH4-10), coadministered (i.c.v.) with 1 microg ACTH1-24, inhibited the ACTH1-24-induced activation of the hypothalamus-pituitary-adrenal-axis and excessive grooming. 3. In addition, several doses of the selective melanocortin-3-receptor agonist Lys-gamma2-MSH were centrally administered, but neither neuroendocrine, nor excessive grooming responses were observed. 4. These results imply that the melanocortin-4-receptor, and not the melanocortin-3-receptor, is involved in the ACTH1-24-induced rise in plasma levels of ACTH and corticosterone, and excessive grooming.

Adrenocorticotropic Hormone↗

PubMed1997

Recovery of function after sciatic nerve crush lesion in rats selected for diverging locomotor activity in the open field.

The relation between recovery of function following a sciatic nerve crush lesion and an individual behavioural characteristic, the locomotor activity in an open field, was investigated in rats. Ten high-active (HA) and ten low-active (LA) rats were selected from a stock of sixty male, random-bred Wistar rats, by measuring travelled distance in an open field. Subsequently, both HA and LA rats underwent an unilateral sciatic nerve crush. Recovery of motor function revealed no significant differences between both groups, whereas recovery of sensory function in HA rats was significantly more rapid than in the LA rats (P < 0.01). These observations suggest the existence of a relationship between individual behavioural characteristics, and the sensory recovery of nerve function following crush lesion in rats.

Adrenal Glands↗

PubMed1997

Proconvulsive effect of vasopressin; mediation by a putative V2 receptor subtype in the central nervous system.

Subcutaneously (s.c.) administered [Arg8]vasopressin (AVP) potentiated seizures induced by intracerebroventricular (i.c.v.) injection of 1.95 mg pilocarpine (a muscarinic cholinergic agonist). A bell-shaped relation between dose and effect was found. I.c.v. pretreatment with a V1, V2 or oxytocin receptor antagonist was performed to determine whether and what type of receptor is involved in this proconvulsive effect of vasopressin. For these experiments a higher dose of pilocarpine (2.4 mg i.c.v.) was injected. This caused seizures in a slightly but not significantly higher percentage of the rats. A dose-dependent protective action of the V2 receptor antagonist d(CH2),[D-Ile2,Ile4]AVP (effective doses were 25 and 125 ng) on seizures was found. A reduction was observed in the number of animals that developed tonic-clonic convulsions. Neither the V1 receptor antagonist d(CH2)5[Tyr(Me)2]AVP nor the oxytocin receptor antagonist desGly(NH2)9d(CH2)5[Tyr(Me)2Thr4]OVT possessed anti-convulsive activity. Subsequently the type of receptor was studied in detail with fragments of AVP with either V1 or V2 activity. AVP (with V1 and V2 affinity) (1 and 3 microg s.c.) potentiated pilocarpine (1.95 mg) induced seizures. Vasotocin and oxytocin were without effect. Interestingly neither s.c. nor i.c.v. administration of the selective kidney type vasopressin receptor (V2) agonist dDAVP potentiated pilocarpine induced seizures. Several selective antidiuretic agonists (V2), such as d[Val4]AVP, d[Phe2,Val4,D-Arg8]vasopressin (3 microg), [Val4,D-Arg8]vasopressin (3 microg) and d[Val4,D-Arg8]vasopressin (3 microg) were active. Other selective antidiuretic compounds, such as [Val4]AVP, dAVP, d[Tyr(Me)2]AVP and HO[D-Arg8]vasopressin (3 microg) did not influence seizures. These results demonstrate that a combination of substitution of aminoacid 4 (Gln) by Val and to a lesser extent deamination and the D-arginine form yield an active molecule, which can potentiate pilocarpine induced seizures and suggest the existence of a V2 receptor subtype in the brain.

Animals↗

PubMed1997

Behavioural and intestinal responses to novelty in rats selected for diverging reactivity in the open field test.

There are indications that the severity of functional gastrointestinal disturbances in humans is linked to individual coping styles. In rodents, the open field test can be used to assess individual differences in behavioural responsivity to novel challenges. Two groups of Wistar rats were selected for high (HA) and low (LA) locomotor activity in a novel open field and fitted with electrodes on the proximal colon. During subsequent exposure to a novel box, a smaller locomotor activation in LA was accompanied by a greater increase in colonic spike burst activity compared to HA rats, even though this novel stressful challenge did not result in a clear defecation response in either group. In contrast, no marked behavioural differences between HA and LA were seen in the shock prod paradigm. Although detection of divergent behavioural responsivity in HA and LA rats may depend on stimulus quality or intensity, combined use of behavioural selection and intestinal motility recording in freely moving rats may offer a model to study individual vulnerability to stress-related disturbances of intestinal function.

Action Potentials↗

PubMed1996

Sensitization of the colonic response to novel stress after previous stressful experience.

Stressful life events may be important causative or precipitating factors for functional gastrointestinal disorders such as the irritable bowel syndrome in humans. In the rat, a single session of foot shocks is known to sensitize the behavioral and hormonal responses to subsequent stress, but intestinal responses have not been investigated. Rats were fitted with bipolar electrodes on proximal colon and exposed to a single session of foot shocks (10 x 6 s in 15 min; preshocked) or no shocks (control). Weight gain after foot shocks was identical to that in controls. Two weeks after foot shocks, basal colonic spike burst frequency did not differ from controls or from that recorded before shock treatment. Unlike controls, however, preshocked rats showed a significant increase in colonic spike burst frequency to a novel stressful challenge in the home cage, an electrified prod. Because the behavioral responses to this challenge did not differ, colonic hyperresponsiveness in preshocked rats may represent a form of stress-induced autonomic sensitization. The model should be a useful tool to study mechanisms and pharmacotherapeutic approaches of the gastrointestinal consequences of traumatic stress.

Animals↗

PubMed1995

Effects of novelty and conditioned fear on small intestinal and colonic motility and behaviour in the rat.

Novelty and conditioned fear were used to investigate the effects of psychological stress on fasting small intestinal and colonic myoelectric activity and their relation with behaviour in freely moving rats fitted with bipolar electrodes on proximal jejunum and colon. Rats in both novelty and conditioned fear groups spent a 15 min session in a novel box, where only rats in the fear group received unescapable, repeated foot shock (10 x 6 s, 0.5 mA). Behaviour in groups reexposed to the box on day 1 or day 7 indicated a profound difference in emotional state. Conditioned fear rats remained largely immobile, while novelty rats displayed active exploratory behaviour. Behaviour during conditioned fear did not differ significantly between rats reexposed to the box either 1 or 7 days after foot shock, while novelty animals appeared more aroused on day 7. Conditioned fear on day 1 caused a significant increase in colonic spike burst frequency compared to basal values in the home cage. A smaller but significant increase was found in novelty rats. In groups tested after 7 days, both novelty and conditioned fear resulted in small increases in colonic burst frequency that did not differ significantly from each other. No effects were found on the incidence of the fasting jejunal Migrating Motility Complex. Defecation was see only in conditioned fear rats, but did not differ quantitatively between day 1 and day 7. We conclude that, in the rat, colonic myoelectric spike burst activity is highly responsive to psychological stress, while the fasting pattern of small intestinal activity is more resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

A long-lasting increase and decrease in synaptic excitability in the rat lateral septum are associated with high and low shuttle box performance, respectively.

In a series of experiments with rats, using evoked field potentials, the influence of massed trial training in 2-way shuttle box avoidance and step-through passive avoidance tasks was studied on the synaptic excitability of the lateral septum (LS) neurons and on the induction of long-term potentiation in the lateral septum in vivo. The majority of rats that attained a high performance level in the shuttle box task exhibited, after the shuttle box training, a long-lasting enhancement of synaptic excitability of lateral septum neurons, whereas most of the rats with low performance in the shuttle box showed a long-lasting depression in the LS synaptic excitability. Both types of excitability changes disappeared within 24 h. Neither the first habituation session in the passive avoidance apparatus nor the subsequent one-trial learning in passive avoidance task had a marked influence on lateral septum synaptic excitability. Both high-performance and low-performance rats exhibited a long-term potentiation (LTP)-like potentiation of synaptic excitability of the lateral septum neurons after high frequency stimulation of the fimbria fibers although the amount of LTP in high performance rats was slightly higher than that in low performance animals.

Animals↗

PubMed1995

Computer analysis of the migrating motility complex of the small intestine recorded in freely moving rats.

Myoelectric activity of the small intestine was recorded digitally in fasted, freely moving rats fitted with multiple pairs of electrodes in the antimesenterial smooth muscle. The electrodes were implanted under strict aseptic conditions to safeguard the animal's health and thereby benefit experimental results. As in many other mammalian species, the fasted electrical and mechanical activity of the small intestine in the rat consists of alternating periods of activity and quiescence jointly called the Migrating Motility Complex (MMC). Existing methods for the analysis of small bowel myoelectric activity either integrate spike activity over longer periods of time or describe characteristics of single bursts. We have developed a computer program for fast, automated analysis that distinguishes the three characteristic phases of the MMC. The computer program recognizes periods of varying spike burst frequency and then produces a graphical and numerical output of the length and mean burst frequency of the different phases of each MMC that correlates well with the results of visual evaluation. The techniques used are discussed in relation to existing recording and analysis methods, and specific decisions in the program are motivated. The system will be a useful tool in assessing the effects of drugs, peptides, or stress on small bowel motility.

Animals↗

PubMed1993

Differential effects of corticosteroids on rat peripheral blood T-lymphocyte mitogenesis in vivo and in vitro.

The effects of corticosteroids were studied on the concanavalin A (Con A)-induced mitogenesis of peripheral blood T-lymphocytes obtained from intact and adrenalectomized (ADX) Wistar rats. One week of adrenalectomy reduced the proliferative response of T-cells by 65% compared with sham-operated controls. Substitution of ADX rats with subcutaneously implanted 12.5-mg corticosterone (Cort) pellets, which resulted in low circulating Cort levels (17 +/- 3 nM), restored the reduced proliferative capacity to that of sham-ADX animals. In contrast, T-lymphocyte proliferation was nearly absent in ADX rats substituted with high circulating Cort levels (173 +/- 15 nM; 100-mg Cort pellet). In vitro, Cort suppressed the mitogenic response of T-lymphocytes from ADX and sham-ADX animals. The glucocorticoid antagonist RU-486 (500 nM) completely blocked this suppressive effect. However, a 10 times lower concentration of RU-486 reversed the effects of a low (10 nM) Cort concentration from suppression to stimulation. It is concluded that high Cort concentrations in vivo and in vitro suppressed T-lymphocyte mitogenesis but that low concentrations in vivo were stimulatory, whereas this stimulation in vitro occurred only in the presence of antiglucocorticoids. These opposing effects of Cort emphasize a bimodal regulatory role of this hormone in immune regulation that may be mediated by different corticosteroid receptors.

Adrenalectomy↗