Glucocorticoid-mediated responses of plasma ACTH and anterior pituitary pro-opiomelanocortin, growth hormone and prolactin mRNAs during adjuvant-induced arthritis in the rat

1992 ◽  
Vol 9 (3) ◽  
pp. 273-281 ◽  
Author(s):  
A. Stephanou ◽  
N. J. Sarlis ◽  
R. A. Knight ◽  
S. L. Lightman ◽  
H. S. Chowdrey
Keyword(s):  
Mrna Expression ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Anterior Pituitary ◽  
Feedback Inhibition ◽  
Feedback Effect ◽  
High Dose ◽  
Plasma Acth ◽  
Pomc Mrna ◽  
Prolactin Mrna

ABSTRACT Adjuvant arthritis (AA) in the rat leads to chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the loss of its diurnal rhythmicity. We have investigated the effects of adrenalectomy (ADX) and different levels of corticosterone replacement upon plasma ACTH levels and anterior pituitary pro-opiomelanocortin (POMC), GH and prolactin mRNAs during the development of AA. In control ADX animals, we observed the negative feedback effects of exogenous corticosterone on plasma ACTH and anterior pituitary POMC mRNA. In the ADX animal with AA, however, the increased POMC mRNA which was observed was not reduced by exogenous corticosterone on day 7 of AA, although the negative feedback effect of corticosterone on plasma ACTH was intact. On day 14, however, even high dose corticosterone replacement failed to have a significant feedback effect on the raised levels of plasma ACTH. In control ADX animals, corticosterone replacement resulted in increased anterior pituitary GH mRNA and reduced prolactin mRNA. In contrast, in ADX animals with AA, GH mRNA was reduced and there was a further decrease in prolactin mRNA. In these animals, corticosterone replacement did not affect GH or prolactin mRNA expression. These data demonstrate a disruption of the normal mechanisms underlying feedback inhibition of the HPA axis by glucocorticoids during AA. Similarly, the glucocorticoid-dependent regulation of GH and prolactin mRNA expression is altered in AA.

scholarly journals Effect of salsolinol on ACTH and cortisol response to handling stress in early anestrous sheep

2017 ◽  
Vol 62 (No. 3) ◽  
pp. 130-139 ◽  
Author(s):  
M. Hasiec ◽  
M. Szlis ◽  
N. Chmielewska ◽  
K. Górski ◽  
K. Romanowicz ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hpa Axis ◽  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Plasma Prolactin ◽  
Plasma Acth ◽  
Handling Stress ◽  
Response To Stress ◽  
Intracerebroventricular Injections ◽  
Cortisol Release

Inhibition of hypothalamic–pituitary–adrenal (HPA) axis activity by salsolinol was demonstrated in lactating sheep. We assessed whether salsolinol regulates, besides lactation, also adrenocorticotropic hormone (ACTH) and cortisol release, and if its action is prolactin-dependent. We examined two groups of early anestrous sheep, which received for three days salsolinol or vehicle-only intracerebroventricular injections, and a group of lactating sheep injected with the vehicle only. On day 3, blood samples were collected for over six hours and the anterior pituitary was dissected. Plasma ACTH, cortisol, and prolactin concentrations, and proopiomelanocortin (POMC) and prolactin (PRL) mRNA expression within the anterior pituitary were assayed. In all groups, ACTH and cortisol concentrations were higher (P < 0.05 and P < 0.001) during the first half of sampling than in the second half; there were no differences in prolactin concentration. Lactating sheep had lower (P < 0.05 and P < 0.001) plasma ACTH and cortisol concentrations and higher (P < 0.001) plasma prolactin concentration than both groups of anestrous sheep during the first half of sampling. In the second half, there were no differences in ACTH and cortisol concentrations between all groups, but prolactin concentration was still higher (P < 0.001) in lactating animals. Salsolinol treatment decreased ACTH and cortisol concentrations during the first half of sampling (P < 0.05 and P < 0.001) compared to the anestrous controls, but had no effect on prolactin concentration. POMC mRNA expression was lower (P < 0.05) and PRL mRNA expression was higher (P < 0.05) in lactating sheep than in anestrous sheep. Salsolinol did not affect POMC and PRL mRNA expression. In conclusion, increased ACTH and cortisol concentrations during the first half of sampling occurred in response to handling stress. Salsolinol inhibited the HPA axis response to stress in early anestrous sheep, and it was unrelated to prolactin secretion.

scholarly journals Plasma leptin and ghrelin in the neonatal rat: interaction of dexamethasone and hypoxia

2005 ◽  
Vol 185 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Eric D Bruder ◽  
Lauren Jacobson ◽  
Hershel Raff
Keyword(s):  
Mrna Expression ◽  
Energy Homeostasis ◽  
Metabolic Stress ◽  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Plasma Acth ◽  
Pomc Mrna ◽  
And Shifts ◽  
Plasma Leptin ◽  
Pituitary Adrenal Axis

Ghrelin, leptin, and endogenous glucocorticoids play a role in appetite regulation, energy balance, and growth. The present study assessed the effects of dexamethasone (DEX) on these hormones, and on ACTH and pituitary proopiomelanocortin (POMC) and corticotropin-releasing hormone receptor-1 (CRHR1) mRNA expression, during a common metabolic stress – neonatal hypoxia. Newborn rats were raised in room air (21% O2) or under normobaric hypoxia (12% O2) from birth to postnatal day (PD) 7. DEX was administered on PD3 (0.5 mg/kg), PD4 (0.25 mg/kg), PD5 (0.125 mg/kg), and PD6 (0.05 mg/kg). Pups were studied on PD7 (24 h after the last dose of DEX). DEX significantly increased plasma leptin and ghrelin in normoxic pups, but only increased ghrelin in hypoxic pups. Hypoxia alone resulted in a small increase in plasma leptin. Plasma corticosterone and pituitary POMC mRNA expression were decreased 24 h following the last dose of DEX, whereas plasma ACTH and pituitary CRHR1 mRNA expression had already increased (normoxia and hypoxia). Hypoxia alone increased corticosterone, but had no effect on ACTH or pituitary POMC and CRHR1 mRNA expression. Neonatal DEX treatment, hypoxia, and the combination of both affect hormones involved in energy homeostasis. Pituitary function in the neonate was quickly restored following DEX-induced suppression of the hypothalamic–pituitary–adrenal axis. The changes in ghrelin, leptin, and corticosterone may be beneficial to the hypoxic neonate through the maintenance of appetite and shifts in intermediary metabolism.

scholarly journals Hypoactivity of the Hypothalamo-Pituitary-Adrenocortical Axis during Recovery from Chronic Variable Stress

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 2008-2017 ◽  
Author(s):  
Michelle M. Ostrander ◽  
Yvonne M. Ulrich-Lai ◽  
Dennis C. Choi ◽  
Neil M. Richtand ◽  
James P. Herman
Keyword(s):  
Mrna Expression ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Male Rats ◽  
Plasma Acth ◽  
Novel Environment ◽  
Systemic Hypoxia ◽  
Delayed Recovery ◽  
Chronic Variable Stress

Chronic stress induces both functional and structural adaptations within the hypothalamo-pituitary-adrenocortical (HPA) axis, suggestive of long-term alterations in neuroendocrine reactivity to subsequent stressors. We hypothesized that prior chronic stress would produce persistent enhancement of HPA axis reactivity to novel stressors. Adult male rats were exposed to chronic variable stress (CVS) for 1 wk and allowed to recover. Plasma ACTH and corticosterone levels were measured in control or CVS rats exposed to novel psychogenic (novel environment or restraint) or systemic (hypoxia) stressors at 16 h, 4 d, 7 d, or 30 d after CVS cessation. Plasma ACTH and corticosterone responses to psychogenic stressors were attenuated at 4 d (novel environment and restraint) and 7 d (novel environment only) recovery from CVS, whereas hormonal responses to the systemic stressor were largely unaffected by CVS. CRH mRNA expression was up-regulated in the paraventricular nucleus of the hypothalamus (PVN) at 16 h after cessation of CVS, but no other alterations in PVN CRH or arginine vasopressin mRNA expression were observed. Thus, in contrast to our hypothesis, reductions of HPA axis sensitivity to psychogenic stressors manifested at delayed recovery time points after CVS. The capacity of the HPA axis to respond to a systemic stressor appeared largely intact during recovery from CVS. These data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.

scholarly journals Corticotropin Secretory Dynamics in Humans under Low Glucocorticoid Feedback

2001 ◽  
Vol 86 (11) ◽  
pp. 5554-5563 ◽  
Author(s):  
J. D. Veldhuis ◽  
A. Iranmanesh ◽  
D. Naftolowitz ◽  
N. Tatham ◽  
F. Cassidy ◽  
...  
Keyword(s):  
Negative Feedback ◽  
High Dose ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Burst Frequency ◽  
Feedback Controls ◽  
Release Process ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis ◽  
Acth Release

To explore the mechanisms of homeostatic adaptation of the hypothalamo-pituitary-adrenal axis to an experimental low-feedback condition, we quantitated pulsatile (ultradian), entropic (pattern-sensitive), and 24-h rhythmic (circadian) ACTH secretion during high-dose metyrapone blockade (2 g orally every 2 h for 12 h, and then 1 g every 2 h for 12 h). Plasma ACTH and cortisol concentrations were sampled concurrently every 10 min for 24 h in nine adults. The metyrapone regimen reduced the amplitude of nyctohemeral cortisol rhythm by 45% (P = 0.0013) and delayed the time of the cortisol maximum (acrophase) by 7.1 h (P = 0.0002). Attenuated cortisol negative feedback stimulated a 7-fold increase in the mean (24-h) plasma ACTH concentration, which rose from 24 ± 1.6 to 169± 31 pg/ml (ng/liter) (P < 0.0001). Augmented ACTH output was driven by a 12-fold amplification of ACTH secretory burst mass (integral of the underlying secretory pulse) (21 ± 3.1 to 255 ± 64 pg/ml; P < 0.0001), yielding a higher percentage of ACTH secreted in pulses (53 ± 3.5 vs. 92 ± 1.3%; P < 0.0001). There were minimal elevations in basal (nonpulsatile) ACTH secretion (by 50%; P = 0.0049) and ACTH secretory burst frequency (by 36%; P = 0.031). The estimated half-life of ACTH (median, 22 min) and the calculated ACTH secretory burst half-duration (pulse event duration at half-maximal amplitude) (median, 23 min) did not change. Hypocortisolemia evoked remarkably more orderly subordinate patterns of serial ACTH release, as quantitated by the approximate entropy statistic (P= 0.003). This finding was explained by enhanced regularity of successive ACTH secretory pulse mass values (P = 0.032). In contrast, there was no alteration in serial ACTH interpulse-interval (waiting-time) regularity. At the level of 24-h ACTH rhythmicity, cortisol withdrawal enhanced the daily rhythm in ACTH secretory burst mass by 29-fold, elevated the mesor by 16-fold, and delayed the acrophase by 3.4 h from 0831 h to 1154 h (each P < 10−3). In summary, short-term glucocorticoid feedback deprivation primarily (>97% of effect) amplifies pulsatile ACTH secretory burst mass, while minimally elevating basal/nonpulsatile ACTH secretion and ACTH pulse frequency. Reduced cortisol feedback paradoxically elicits more orderly (less entropic) patterns of ACTH release due to emergence of more regular ACTH pulse mass sequences. Cortisol withdrawal concurrently heightens the amplitude and mesor of 24-h rhythmic ACTH release and delays the timing of the ACTH acrophase. In contrast, the duration of underlying ACTH secretory episodes is not affected, which indicates that normal pulse termination may be programmed centrally rather than imposed by rapid negative feedback. Accordingly, we hypothesize that adrenal glucocorticoid negative feedback controls hypothalamo-pituitary-adrenal axis dynamics via the 3-fold distinct mechanisms of repressing the mass of ACTH secretory bursts, reducing the orderliness of the corticotrope release process, and modulating the intrinsic diurnal rhythmicity of the hypothalamo-corticotrope unit.

Dexamethasone inhibits ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), and oCRF + AVP stimulated release of ACTH during the last third of pregnancy in the sheep fetus

1987 ◽  
Vol 65 (6) ◽  
pp. 1186-1192 ◽  
Author(s):  
Laurie J. Norman ◽  
John R. G. Challis
Keyword(s):  
Negative Feedback ◽  
Arginine Vasopressin ◽  
Late Pregnancy ◽  
Feedback Effect ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Corticotrophin Releasing Factor ◽  
Basal Release ◽  
Sheep Fetus ◽  
Acth Release

We examined the hypothesis that in fetal sheep during late pregnancy exogenous glucocorticoids might affect differentially the pituitary response, measured as changes in plasma ACTH concentrations, to the systemic administration of ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), or oCRF + AVP. At d 113–116 of pregnancy, equimolar injections of oCRF and AVP given separately provoked similar significant increases in plasma ACTH; the change in ACTH over basal values was significantly greater than the sum of the two separate responses when AVP + oCRF were given together. Exogenous dexamethasone did not affect basal ACTH concentrations, but suppressed significantly the responses to oCRF, AVP, and oCRF + AVP. At d 126–130, there was a significant ACTH response to CRF alone and to AVP + oCRF, but not to AVP alone. The response during the first 30 min postinjection to oCRF was significantly less than that to AVP + oCRF. Plasma Cortisol rose after each peptide injection. Exogenous dexamethasone suppressed both basal and stimulated responses to each peptide. At the amounts injected, there was no significant ACTH or Cortisol response to oCRF, AVP, or oCRF + AVP at d 136–140, but dexamethasone suppressed basal ACTH and Cortisol concentrations at this time. We conclude that stimulated, but not basal, release of ACTH is subject to the negative feedback effect of exogenous glucocorticoid by d 113–116 of gestation in fetal sheep. Both basal and stimulated release of ACTH and Cortisol are suppressed after d 125. At the amount of exogenous dexamethasone given, oCRF, AVP, and oCRF + AVP-stimulated responses are affected similarly. Our results suggest different controls of basal and stimulated ACTH release from the pituitary at d 113–116 of gestation. Our findings would be consistent with the pituitary as a level of action for the negative feedback effect of corticosteroids on stimulated ACTH release throughout the last third of pregnancy in fetal sheep.

scholarly journals Allopregnanolone reduces neuroendocrine response to acute stressful stimuli in sheep

2020 ◽  
Vol 244 (1) ◽  
pp. 201-211 ◽  
Author(s):  
Tomasz Misztal ◽  
Patrycja Młotkowska ◽  
Elżbieta Marciniak ◽  
Anna Misztal
Keyword(s):  
Hpa Axis ◽  
Adrenocorticotropic Hormone ◽  
Plasma Sample ◽  
Sample Collection ◽  
Plasma Acth ◽  
Movement Restriction ◽  
Stress Control ◽  
Pomc Mrna ◽  
Collection Period ◽  
Hpa Axis Activity

The verified hypothesis assumed that centrally administered neurosteroid, allopregnanolone (AL), could affect basal and/or stress-induced activity of the hypothalamic-pituitary-adrenal (HPA) axis in sheep. Four groups (n = 6 each) of luteal-phase sheep were intracerebroventricularly infused for 3 days with a vehicle without stress (control); a vehicle treated with stressful stimuli (isolation and partial movement restriction) on the third day; AL (4 × 15 µg/60 µL/30 min, at 30-min intervals) treated with stressful stimuli, and AL alone. Simultaneously, the push-pull perfusion of the infundibular nucleus/median eminence and plasma sample collection were performed. After the experiment, the sheep were killed to collect the hypothalamic and anterior pituitary (AP) tissues. Stressful stimuli evoked an increase in the expression of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the hypothalamic paraventricular nucleus (PVN), and AVP receptor (V1b) and proopiomelanocortin (POMC) mRNA in the AP; the concentrations of perfusate CRH, and plasma adrenocorticotropic hormone (ACTH) and cortisol compared to controls. Conversely, the expression of the CRH receptor (CRHR1) mRNA in the AP was downregulated. AL decreased the expression of CRH and AVP mRNA in the PVN, and AVPRV1b and POMC mRNA in the AP in stressed sheep, compared to only stressed ones. There was also a reduction in perfusate CRH, and plasma ACTH and cortisol concentrations. AL alone decreased the expression of CRHR1 mRNA in the AP, and plasma cortisol concentration at the beginning of the collection period compared to controls. In conclusion, AL may function centrally as a suppressor of HPA axis activity in stressed sheep.

scholarly journals Differential involvement of adrenal and gonadal steroids in anterior and intermediate pituitary pro-opiomelanocortin mRNA expression induced by the endogenous benzodiazepine, octadecaneuropeptide, in adult male rats

1999 ◽  
Vol 161 (2) ◽  
pp. 307-316 ◽  
Author(s):  
L Givalois ◽  
S Li ◽  
G Pelletier
Keyword(s):  
Mrna Expression ◽  
Anterior Pituitary ◽  
Gonadal Steroids ◽  
Male Rats ◽  
Hybridization Signal ◽  
Hybridization Technique ◽  
Intermediate Lobe ◽  
Pomc Mrna ◽  
Control Sham

The involvement of the endogenous benzodiazepine, octadecaneuropeptide (ODN), in the regulation of proopiomelanocortin (POMC) mRNA expression at the pituitary level, and the influence of adrenal and gonadal steroids, have been studied using a quantitative in situ hybridization technique. I.c.v. injection of ODN (4 micrograms/kg) in sham-operated rats induced a 17 and 7% decrease in the POMC mRNA expression in anterior and intermediate pituitary lobes respectively. To determine the reciprocal involvement of adrenal and gonadal steroids in this regulation, animals were adrenalectomized and/or castrated. Adrenalectomy significantly increased POMC mRNA expression by 48% at the anterior pituitary level, but induced a 10% decrease of hybridization signal at the intermediate pituitary lobe (vs control sham-operated). Adrenal ablation reversed the effect induced by ODN and increased POMC mRNA expression at the anterior and intermediate pituitary levels by 60 and 10% respectively, compared with control sham-operated. By contrast, castration, which produced a decrease in POMC mRNA in the anterior pituitary and an increase in the intermediate lobe, did not modify the negative influence of ODN observed in sham-operated animals. When rats were adrenalectomized and castrated, the adrenalectomy influence was predominant at the anterior pituitary level, since ODN increased significantly the hybridization signal (+68% vs control sham-operated), while the castration influence was predominant at the intermediate pituitary level, since ODN induced an 11% decrease in POMC mRNA signal compared with control sham-operated. These studies indicate that, in vivo, the decrease in POMC mRNA expression in the anterior and intermediate pituitary induced by an endogenous benzodiazepine is differently modulated by adrenal and gonadal steroids, with a predominant influence of adrenal steroids at the anterior pituitary level and gonadal steroids at the intermediate pituitary level.

NEGATIVE, RATE-SENSITIVE FEEDBACK EFFECTS ON ADRENOCORTICOTROPHIN SECRETION BY CORTISOL IN NORMAL SUBJECTS

1982 ◽  
Vol 92 (3) ◽  
pp. 443-448 ◽  
Author(s):  
S. C. J. READER ◽  
J. ALAGHBAND-ZADEH ◽  
J. R. DALY ◽  
W. R. ROBERTSON
Keyword(s):  
Negative Feedback ◽  
Feedback Inhibition ◽  
Fast Rate ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Stress Tests ◽  
Nacl Solution ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Feedback Effects

Plasma ACTH and corticosteroid levels were measured in normal subjects during constant infusion of either 0·9% (w/v) NaCl solution or cortisol, and during insulin-induced hypoglycaemia. During infusions of 0·9% NaCl solution the secretion of ACTH and corticosteroids was episodic. Fast, rate-sensitive, negative feedback inhibition of ACTH secretion was observed during cortisol infusions, when the corticosteroid levels were within the physiological range (200–750 nmol/l) and were rising at a rate of between 5 and 10 nmol/l per min for 30 min or longer. When plasma corticosteroid levels were in a steady state, the initial fast feedback effects were abolished and ACTH secretion resumed. However, this recovery of ACTH secretion was not seen when the corticosteroid levels were persistently above 800 nmol/l. It appears that corticosteroid-induced negative feedback in man may be both rate- and level-sensitive. During insulin stress tests ACTH secretion fell at a time when the plasma corticosteroid level was rising rapidly (> 5 nmol/l per min) despite persistent hypoglycaemia.

scholarly journals Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4811-4819 ◽  
Author(s):  
Nathan K. Evanson ◽  
Jeffrey G. Tasker ◽  
Matthew N. Hill ◽  
Cecilia J. Hillard ◽  
James P. Herman
Keyword(s):  
Hpa Axis ◽  
Negative Feedback ◽  
Stress Responses ◽  
Feedback Inhibition ◽  
Signaling Mechanism ◽  
Hypothalamic Tissue ◽  
Corticosterone Release ◽  
Arachidonoyl Glycerol ◽  
Local Release ◽  
Glucocorticoid Action

Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN). Local infusion of dexamethasone or a membrane-impermeant dexamethasone-BSA conjugate into the PVN rapidly inhibits restraint-induced ACTH and corticosterone release in a manner consistent with feedback actions at the cell membrane. The dexamethasone fast feedback response is blocked by the cannabinoid CB1 receptor antagonist AM-251, suggesting that fast feedback requires local release of endocannabinoids. Hypothalamic tissue content of the endocannabinoid 2-arachidonoyl glycerol is elevated by restraint stress, consistent with endocannabinoid action on feedback processes. These data support the hypothesis that glucocorticoid-induced fast feedback inhibition of the HPA axis is mediated by a nongenomic signaling mechanism that involves endocannabinoid signaling at the level of the PVN.

scholarly journals Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus

2018 ◽  
Vol 8 (10) ◽  
pp. 184 ◽  
Author(s):  
Grace Pham ◽  
Keisa Mathis
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Hpa Axis ◽  
Lupus Erythematosus ◽  
Anterior Pituitary ◽  
Plasma Corticosterone ◽  
Innate Immune ◽  
Systemic Lupus ◽  
Plasma Acth ◽  
Lps Challenge ◽  
Fos Expression

Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation.

Sign in / Sign up

Export Citation Format

Share Document