Adrenocorticotropic hormone and corticosterone responses to acute hypoxia in the neonatal rat: effects of body temperature maintenance

2011 ◽  
Vol 300 (3) ◽  
pp. R708-R715 ◽  
Author(s):  
Eric D. Bruder ◽  
Kimberli J. Kamer ◽  
Mitchell A. Guenther ◽  
Hershel Raff
Keyword(s):  
Stress Response ◽  
Body Temperature ◽  
Acute Hypoxia ◽  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Plasma Acth ◽  
Neonatal Hypoxia ◽  
Rat Pups ◽  
Expression Of Genes ◽  
Corticosterone Response

The corticosterone response to acute hypoxia in neonatal rats develops in the 1st wk of life, with a shift from ACTH independence to ACTH dependence. Acute hypoxia also leads to hypothermia, which may be protective. There is little information about the endocrine effects of body temperature maintenance during periods of neonatal hypoxia. We hypothesized that prevention of hypothermia during neonatal hypoxia would augment the adrenocortical stress response. Rat pups separated from their dams were studied at postnatal days 2 and 8 ( PD2 and PD8). In one group of pups, body temperature was allowed to spontaneously decrease during a 30-min prehypoxia period. Pups were then exposed to 8% O2 for 3 h and allowed to become spontaneously hypothermic or externally warmed (via servo-controlled heat) to maintain isothermia. In another group, external warming was used to maintain isothermia during the prehypoxia period, and then hypoxia with or without isothermia was applied. Plasma ACTH and corticosterone and mRNA expression of genes for upstream proteins involved in the steroidogenic pathway were measured. Maintenance of isothermia during the prehypoxia period increased baseline plasma ACTH at both ages. Hypothermic hypoxia caused an increase in plasma corticosterone; this response was augmented by isothermia at PD2, when the response was ACTH-independent, and at PD8, when the response was ACTH-dependent. In PD8 rats, isothermia also augmented the plasma ACTH response to hypoxia. We conclude that maintenance of isothermia augments the adrenocortical response to acute hypoxia in the neonate. Prevention of hypothermia may increase the stress response during neonatal hypoxia, becoming more pronounced with increased age.

scholarly journals Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat

2008 ◽  
Vol 295 (4) ◽  
pp. R1195-R1203 ◽  
Author(s):  
Eric D. Bruder ◽  
Jennifer K. Taylor ◽  
Kimberli J. Kamer ◽  
Hershel Raff
Keyword(s):  
Body Temperature ◽  
Acute Hypoxia ◽  
Age Groups ◽  
Thermal Response ◽  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Severe Hypoxia ◽  
Developmentally Regulated ◽  
Specific Proteins ◽  
Corticosterone Response

Acute episodes of severe hypoxia are among the most common stressors in neonates. An understanding of the development of the physiological response to acute hypoxia will help improve clinical interventions. The present study measured ACTH and corticosterone responses to acute, severe hypoxia (8% inspired O2 for 4 h) in neonatal rats at postnatal days (PD) 2, 5, and 8. Expression of specific hypothalamic, anterior pituitary, and adrenocortical mRNAs was assessed by real-time PCR, and expression of specific proteins in isolated adrenal mitochondria from adrenal zona fascisulata/reticularis was assessed by immunoblot analyses. Oxygen saturation, heart rate, and body temperature were also measured. Exposure to 8% O2 for as little as 1 h elicited an increase in plasma corticosterone in all age groups studied, with PD2 pups showing the greatest response (∼3 times greater than PD8 pups). Interestingly, the ACTH response to hypoxia was absent in PD2 pups, while plasma ACTH nearly tripled in PD8 pups. Analysis of adrenal mRNA expression revealed a hypoxia-induced increase in Ldlr mRNA at PD2, while both Ldlr and Star mRNA were increased at PD8. Acute hypoxia decreased arterial O2 saturation (SPo2) to ∼80% and also decreased body temperature by 5–6°C. The hypoxic thermal response may contribute to the ACTH and corticosterone response to decreases in oxygen. The present data describe a developmentally regulated, differential corticosterone response to acute hypoxia, shifting from ACTH independence in early life (PD2) to ACTH dependence less than 1 wk later (PD8).

Adrenocortical sensitivity to ACTH in neonatal rats: correlation of corticosterone responses and adrenal cAMP content

2014 ◽  
Vol 307 (3) ◽  
pp. R347-R353 ◽  
Author(s):  
Jonathan Bodager ◽  
Thomas Gessert ◽  
Eric D. Bruder ◽  
Ashley Gehrand ◽  
Hershel Raff
Keyword(s):  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Neonatal Rats ◽  
Plasma Acth ◽  
Camp Content ◽  
Rat Pups ◽  
Adrenal Steroidogenesis ◽  
Corticosterone Response ◽  
High Doses ◽  
Corticosterone Release

A coordinated hypothalamic-pituitary-adrenal axis response is important for the survival of newborns during stress. We have previously shown that prior to postnatal day (PD) 5, neonatal rats exposed to hypoxia (one of the most common stressors effecting premature neonates) exhibit a large corticosterone response with a minimal increase in immunoassayable plasma ACTH and without a detectable increase in adrenal cAMP content (the critical second messenger). To explore the phenomenon of ACTH-stimulated steroidogenesis in the neonate, we investigated the adrenal response to exogenous ACTH in the normoxic neonatal rat. Rat pups at PD2 and PD8 were injected intraperitoneally with porcine ACTH at low, moderate, or high doses (1, 4, or 20 μg/kg body wt). Trunk blood and whole adrenal glands were collected at baseline (before injection) and 15, 30, or 60 min after the injection. ACTH stimulated corticosterone release in PD2 and PD8 pups. In PD2 pups, plasma corticosterone at baseline and during the response to ACTH injection was greater than values measured in PD8 pups, despite lower adrenal cAMP content in PD2 pups. Specifically, the low and moderate physiological ACTH doses produced a large corticosterone response in PD2 pups without a change in adrenal cAMP content. At extremely high, pharmacological levels of plasma ACTH in PD2 pups (exceeding 3,000 pg/ml), an increase in adrenal cAMP was measured. We conclude that physiological increases in plasma ACTH may stimulate adrenal steroidogenesis in PD2 pups through a non-cAMP-mediated pathway.

Pituitary-adrenal response to bacterial endotoxin in developing rats

1988 ◽  
Vol 255 (4) ◽  
pp. E525-E530 ◽  
Author(s):  
L. Witek-Janusek
Keyword(s):  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Bacterial Endotoxin ◽  
Plasma Acth ◽  
Adult Rats ◽  
Age Related ◽  
Corticosterone Response ◽  
Adrenal Response ◽  
Old Rats ◽  
Related Pattern

The neonatal rat is very sensitive to the lethal effects of bacterial endotoxin. Because of the adaptive importance of pituitary-adrenal secretions to stress, this study examined the ontogeny of the plasma corticosterone and adrenocorticotropic hormone (ACTH) responses to endotoxin. The lethal sensitivity of young rats to endotoxin ranged from 0.5 to 30 mg/kg (ip) in the 1- to 21-day-old rat. After endotoxin treatment, the 1- and 2-day-old rat showed marked elevations of corticosterone similar in magnitude to that seen in 21-day-old and adult rats; however, significantly depressed corticosterone increments were observed in the 5-, 10-, and 14-day-old rats. This age-related pattern of adrenocortical secretion was correlated with the developing rat's corticosterone response to exogenous ACTH. In contrast, endotoxin administered to 5-, 10-, and 14-day-old rats resulted in increments of plasma ACTH similar to those observed in the 21-day-old and adult rats. Although plasma ACTH levels increased by 84-127% in the 1- and 2-day-old rats, these increases were significantly less than those of rats at all other ages tested. Thus the newborn rat mounts an effective corticosterone response to endotoxin, loses this ability between ages 5-14 days, and regains this response at 21 days of age. Because the hyporesponsive ages exhibit a marked increase in ACTH secretion, the loss of the adrenocortical response to endotoxin appears to be a result of a depressed responsiveness of the adrenal cortex to ACTH.

Pituitary-adrenal function after transplantation in rats: dependence on age of the adrenal graft

1986 ◽  
Vol 250 (1) ◽  
pp. E87-E93
Author(s):  
W. C. Engeland
Keyword(s):  
Plasma Corticosterone ◽  
Adrenal Function ◽  
Adrenocortical Function ◽  
Elevated Plasma ◽  
Plasma Acth ◽  
Adult Rats ◽  
Adrenal Cells ◽  
Adrenal Tissue ◽  
Corticosterone Response

Comparisons of resting plasma adrenocorticotropin (ACTH) and corticosterone in the morning and afternoon were made among adult rats bearing regenerated adult adrenal grafts, neonatal (day 1) adrenal grafts, adult adrenal capsule grafts, or intact adrenals. In the morning plasma ACTH and corticosterone were similar in all rats. In the afternoon, plasma ACTH was elevated in rats bearing neonatal adrenal grafts or adult adrenal capsule grafts, but not in rats bearing whole adult adrenal grafts. There was no difference in afternoon plasma corticosterone among rats bearing transplanted adrenals, although afternoon plasma corticosterone was decreased in rats bearing transplants compared with rats with intact adrenals. Thus the increased plasma ACTH after adrenal transplantation cannot be explained entirely by decreases in resting plasma corticosterone. Adrenal responsiveness to ACTH was tested at 5 wk after transplantation in the afternoon by measuring the plasma corticosterone response to submaximal doses of ACTH. The responsiveness was decreased in rats bearing transplants. In addition, responsiveness was inversely related to the age of the grafted adrenal tissue. Adrenals regenerated from adult adrenals were more responsive than adrenals regenerated either from neonatal adrenals or from adult adrenal capsules. The findings suggest that following adrenal transplantation reestablishment of normal pituitary-adrenocortical function does not occur in rats bearing adrenals regenerated from immature adrenal cells. In addition, comparable alterations occur after regeneration of adrenal tissue from neonatal adrenal cells and adult adrenal capsular cells. Elevated plasma ACTH associated with adequate plasma corticosterone in rats bearing adrenals regenerated from immature adrenal cells may result from chronic alteration in responsiveness to steroid feedback.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

DEVELOPMENTAL STUDY OF PITUITARY-ADRENOCORTICAL RESPONSE IN MICE: PLASMA AND BRAIN CORTICOSTERONE DETERMINATION AFTER HISTAMINE STRESS

1974 ◽  
Vol 60 (2) ◽  
pp. 353-358 ◽  
Author(s):  
RYOKO KAKIHANA ◽  
STEPHEN BLUM ◽  
SEYMOUR KESSLER
Keyword(s):  
Stress Response ◽  
Subcutaneous Injection ◽  
Plasma Corticosterone ◽  
Developmental Study ◽  
Histamine Dihydrochloride ◽  
Adrenocortical Response ◽  
Corticosterone Response ◽  
Adrenocortical Stress Response ◽  
Hybrid Mice ◽  
The Brain

SUMMARY The development of the pituitary-adrenocortical stress response was studied in CBA/J × DBA/2J hybrid mice. On the basis of the plasma corticosterone response 15 min after a subcutaneous injection of histamine dihydrochloride (50 mg/kg), the first three neonatal weeks could be divided into stress-nonresponsive (3–211 days) and stress-responsive 16–21 days) periods. During the former period, corticosterone levels in the brains of the non-stressed control mice were 63% higher than those of comparable mice during the latter period. Histamine stress significantly increased corticosterone concentrations in the brain during both these periods, but the increase was much greater (88%) during the stress-responsive period than during the stress-nonresponsive period (29%).

Modification of pituitary-adrenal feedback sensitivity in young rats by neonatal treatment with cortisol

1981 ◽  
Vol 96 (2) ◽  
pp. 252-257 ◽  
Author(s):  
M. S. Erskine ◽  
Edward Geller ◽  
Arthur Yuwiler
Keyword(s):  
Body Weight ◽  
Stress Response ◽  
Binding Capacity ◽  
Feedback Regulation ◽  
Plasma Corticosterone ◽  
Neonatal Treatment ◽  
Feedback Sensitivity ◽  
Increased Sensitivity ◽  
Corticosterone Response ◽  
Pre Treatment

Abstract. Neonatal exposure of rats to cortisol acetate was found to alter pituitary-adrenal feedback regulation at 20–25 days of age. Plasma levels of adrenocorticotrophin (ACTH) after ether stress were reduced in cortisol-treated rats pre-treated with 100 μg corticosterone/100 g body weight, while rats given vehicle neonatally did not show suppression of the ACTH response below levels in animals given saline only or not injected as pre-treatments. Neonatal cortisol increased sensitivity to dexamethasone in inhibition of the stress response; cortisol-treated animals had a reduced plasma corticosterone response to stress 3 h after pre-treatment with 1.25, 2.5, 25, or 250 μg dexamethasone/100 g body weight, while the stress response in animals given vehicle neonatally was not inhibited by the lowest dosage of dexamethasone. Neonatal cortisol treatment did not affect corticosteroidbinding globulin (CBG) binding capacity in plasma of 25-day-old animals. Thus, neonatal treatment with cortisol appears to increase feedback sensitivity to circulating corticosteroids at 20–25 days of age.

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

2013 ◽  
Vol 304 (9) ◽  
pp. R782-R789 ◽  
Author(s):  
Kathan Chintamaneni ◽  
Eric D. Bruder ◽  
Hershel Raff
Keyword(s):  
Mrna Expression ◽  
Glucose Homeostasis ◽  
Intermittent Hypoxia ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Tissue Samples ◽  
Rat Pups ◽  
Developmental Age ◽  
Adrenal Response

Apnea, the temporary cessation of respiratory airflow, is a common cause of intermittent hypoxia (IH) in premature infants. We hypothesized that IH elicits a stress response and alters glucose homeostasis in the neonatal rat. Rat pups were studied on postnatal day (PD) 2, 8, 10, 12, and 14. Pups were exposed to normoxia (control) or six cycles consisting of 30-s exposures to hypoxia (FiO2 = 3%) over a 60-min period. Blood samples were obtained at baseline, after the third cycle (∼30 min), and after the sixth cycle (∼60 min). Tissue samples were collected following the sixth cycle. Plasma ACTH, corticosterone, glucose, and insulin were analyzed at all ages. Hypothalamic, pituitary, and adrenal mRNA expression was evaluated by quantitative PCR in PD2, PD8, and PD12 pups. Exposure to IH elicited significant increases in plasma ACTH and corticosterone at all ages studied. The largest increase in corticosterone occurred in PD2 pups, despite only a very small increase in plasma ACTH. This ACTH-independent increase in corticosterone in PD2 pups was associated with increases in adrenal Ldlr and Star mRNA expression. Additionally, IH caused hyperglycemia and hyperinsulinemia at all ages. We conclude that IH elicits a significant pituitary-adrenal response and significantly alters glucose homeostasis. Furthermore, the quantitative and qualitative characteristics of these responses depend on developmental age.

Effects of paraventricular lesions on stimulated ACTH release and CRF in stalk-median eminence of the rat

1981 ◽  
Vol 240 (4) ◽  
pp. E441-E446 ◽  
Author(s):  
G. B. Makara ◽  
E. Stark ◽  
M. Karteszi ◽  
M. Palkovits ◽  
G. Rappay
Keyword(s):  
Median Eminence ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Surgical Trauma ◽  
Acth Level ◽  
Plasma Acth ◽  
Medial Basal Hypothalamus ◽  
Plasma Acth Level ◽  
Basal Plasma ◽  
Corticosterone Response

The effects of destroying the paraventricular nucleus (PVN) of the rat hypothalamus on pituitary-adrenal function were studied. Four days after PVN lesions were placed with a rotating knife, the basal plasma corticosterone level was normal, but the corticosterone response to electrical stimulation of the medial basal hypothalamus, surgical trauma, and ether-venesection stress was significantly inhibited. Four and 8 days after PVN lesioning and adrenalectomy, the basal plasma ACTH level was lower, and the rise of plasma ACTH level elicited by a 3-min ether inhalation was significantly smaller than in the adrenalectomized controls. Corticotropin-releasing factor (CRF) activity in the stalk-median eminence extracts from PVN-lesioned rats was significantly less than in the control extracts. The weight of the adrenals was decreased by both 2 and 4 wk after PVN destruction, and 2 wk after hemiadrenalectomy, the compensatory adrenal hypertrophy was inhibited. The plasma corticosterone response to ether-venesection stress was inhibited only temporarily because it returned to normal by the end of the 4th postoperative week. The results are consistent with the hypothesis that a substantial portion of CRF-containing fibers in the stalk-median eminence region either originate from or run though the PVN or its immediate vicinity.

Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

1994 ◽  
Vol 141 (3) ◽  
pp. 497-503 ◽  
Author(s):  
P J Larsen ◽  
J D Mikkelsen ◽  
D Jessop ◽  
S L Lightman ◽  
H S Chowdrey
Keyword(s):  
Hpa Axis ◽  
Restraint Stress ◽  
Acute Stress ◽  
Monosodium Glutamate ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Acute And Chronic Stress ◽  
Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

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