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).

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.

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.

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.

Effects of body temperature maintenance on glucose, insulin, and corticosterone responses to acute hypoxia in the neonatal rat

2012 ◽  
Vol 302 (5) ◽  
pp. R627-R633 ◽  
Author(s):  
Mitchell A. Guenther ◽  
Eric D. Bruder ◽  
Hershel Raff
Keyword(s):  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Acute Hypoxia ◽  
Insulin Response ◽  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Control Group ◽  
Initial Increase ◽  
Time Control ◽  
Subsequent Decrease

One of the biggest challenges of premature birth is acute hypoxia. Hypothermia during acute hypoxic periods may be beneficial. We hypothesized that prevention of hypothermia during neonatal hypoxia disrupts glucose homeostasis and places additional metabolic challenges on the neonate. Pups at PD2 and PD8 were exposed to 8% O2 for 3 h, during which they were allowed to either spontaneously cool or were kept isothermic. There was also a time control group that was subjected to normoxia and kept isothermic. Plasma glucose, insulin, C-peptide, corticosterone, and catecholamines were measured from samples collected at baseline, 1 h, 2 h, and 3 h. In postnatal day 2 (PD2) rats, hypoxia alone resulted in no change in plasma glucose by 1 h, an increase by 2 h, and a subsequent decrease below baseline values by 3 h. Hypoxia with isothermia in PD2 rats elicited a large increase in plasma insulin at 1 h. In PD8 rats, hypoxia with isothermia resulted in an initial increase in plasma glucose, but by 3 h, glucose had decreased significantly to below baseline levels. Hypoxia with and without isothermia elicited an increase in plasma corticosterone at both ages and an increase in plasma epinephrine in PD8 rats. We conclude that the insulin response to hypoxia in PD8 rats is associated with an increase in glucose similar to an adult; however, insulin responses to hypoxia in PD2 rats were driven by something other than glucose. Prevention of hypothermia during hypoxia further disrupts glucose homeostasis and increases metabolic challenges.

Impaired febrile responses of aging mice are mediated by endogenous lipocortin-1 (annexin-1)

1993 ◽  
Vol 265 (2) ◽  
pp. E289-E297 ◽  
Author(s):  
P. J. Strijbos ◽  
M. A. Horan ◽  
F. Carey ◽  
N. J. Rothwell
Keyword(s):  
Body Temperature ◽  
Interleukin 1 ◽  
Age Groups ◽  
Plasma Corticosterone ◽  
Interleukin 1 Beta ◽  
Febrile Response ◽  
Aged Mice ◽  
Annexin 1 ◽  
Adult Mice ◽  
Age Related

The mechanisms underlying age-related impairments in febrile responses were investigated in female C57Bl/lcrf-a(t) mice. Injection of norepinephrine, to assess total thermogenic capacity, significantly increased oxygen consumption (VO2) in all age groups, although the responses of the aged mice were significantly reduced. Injection of lipopolysaccharide or murine interleukin-1 beta (mIL-1 beta) significantly increased body temperature and VO2 in the young and adult mice but not in the aged mice. The impaired responses to mIL-1 beta in the aged mice were normalized by either injection of the glucocorticoid receptor antagonist RU-38486 or by injection of an antiserum to lipocortin-1 or its purified immunoglobulin G fraction. Injection of prostaglandin E2 significantly increased VO2 and body temperature in all age groups. Resting plasma corticosterone concentrations were significantly elevated in the aged and adult mice, whereas injection of mIL-1 beta significantly raised plasma corticosterone concentrations in all animals. These findings indicate that the impaired febrile response of aged female C57Bl/lcrf-a(t) mice may be caused by increased concentrations and/or sensitivity to endogenous glucocorticoids. The impaired febrile responses of aged mice appear to be mediated by endogenous lipocortin-1.

scholarly journals Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: a challenge against conventional interpretation of the test

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hirotaka Shoji ◽  
Tsuyoshi Miyakawa
Keyword(s):  
Elevated Plus Maze ◽  
Plasma Corticosterone ◽  
Illumination Level ◽  
Test Battery ◽  
Lower Percentage ◽  
Behavioral Tests ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Plus Maze ◽  
Corticosterone Response

AbstractThe elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear. In this study, we investigated the effects of experience with a battery of behavioral tests, the wall color of the closed arms, and illumination level on the behavior and plasma corticosterone responses in the elevated plus maze in male C57BL/6J mice. Mice were either subjected to a series of behavioral tests, including assessments of general health and neurological function, a light/dark transition test, and an open field test, or left undisturbed until the start of the elevated plus maze test. The mice with and without test battery experience were allowed to freely explore the elevated plus maze. The other two independent groups of naïve mice were tested in mazes with closed arms with different wall colors (clear, transparent blue, white, and black) or different illumination levels (5, 100, and 800 lx). Immediately after the test, blood was collected to measure plasma corticosterone concentrations. Mice with test battery experience showed a lower percentage of open arm time and entries and, somewhat paradoxically, had lower plasma corticosterone levels than the mice with no test battery experience. Mice tested in the maze with closed arms with clear walls exhibited higher open arm exploration than mice tested in the maze with closed arms with black walls, while there were no significant differences in plasma corticosterone levels between the different wall color conditions. Illumination levels had no significant effects on any measure. Our results indicate that experience with other behavioral tests and different physical features of the maze affect elevated plus maze behaviors. Increased open arm time and entries are conventionally interpreted as decreased anxiety-like behavior, while other possible interpretations are considered: open arm exploration may reflect heightened anxiety and panic-like reaction to a novel situation under certain conditions. With the possibility of different interpretations, the present findings highlight the need to carefully consider the test conditions in designing experiments and drawing conclusions from the behavioral outcomes in the elevated plus maze test in C57BL/6J mice.

Abstract 9: Temperature-responsive Cell Delivery Biopolymers for Cardiac Tissue Engineering

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Brisa Pena ◽  
Valentina Martinelli ◽  
Susanna Bosi ◽  
Carmen Sucharov ◽  
Mark Jeong ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Body Temperature ◽  
Cell Viability ◽  
Cultured Cells ◽  
Ventricular Myocytes ◽  
3D Culture ◽  
Polymeric Matrix ◽  
Neonatal Rat ◽  
Cell Delivery

Background: Advances in cell therapy and material science have made tissue engineering a promising strategy for heart regeneration. We developed an injectable biomimetic reverse thermal gel (RTG) that is liquid at room temperature but gel-like at body temperature, with the ultimate goal of being able to serve as a vehicle for cell-based delivery (liquid) to targeted tissue areas (gel-phase at 37°C). In this study we tested the suitability of this biomimetic RTG on cell viability. Methods and results: We tested different biomimetic RTG systems with and without the chemical incorporation of lysine. In vitro 3D culture experiments were performed with neonatal rat ventricular myocytes (NRVM) by mixing 3x104 cells with 50 μl of polymeric solution and allowing gel formation at 37°C. The cultured cells were incubated for 21 days. For controls we used NRVMs plated on 2D traditional gelatin coated dishes. We found that the 3D polymeric matrix induces rapid coordinated contraction with improved functionality when compared with standard 2D-cultured NRVM. By immunostaining for the morphology of the sarcomere (alpha-actinin) and DAPI, we also observed that the 3D polymeric matrix stimulates cells to spread and form 3D syncytia. Conclusion: These proof-of-concept results demonstrate long-term cell viability in this unique biomimetic system and therefore provide feasibility of a polymeric cell delivery system that permits reversible liquid-to-gel transition at body temperature. These results offer potential for a tissue engineering approach to cardiac regeneration.

Adrenocortical function in aging exercise-trained rats

1977 ◽  
Vol 43 (5) ◽  
pp. 839-843 ◽  
Author(s):  
J. A. Severson ◽  
R. D. Fell ◽  
J. G. Tuig ◽  
D. R. Griffith
Keyword(s):  
Age Groups ◽  
Plasma Corticosterone ◽  
Treadmill Running ◽  
Adrenocortical Function ◽  
Elevated Plasma ◽  
Corticosterone Concentration ◽  
Relationship Of ◽  
The Relationship

Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone were determined in exercise-trained rats. Rats, 100, 200, and 300 days of age, were trained for a 10-wk period by treadmill running. Following the training program, rats were subjected to an acute bout of swimming. Acute swimming elevated plasma corticosterone concentrations in all age groups. At 170 days of age, the plasma corticosterone concentration following swimming was higher in exercise-trained rats than in controls. The opposite was true of acutely swum rats at 270 and 370 days of age. Acute swimming elevated the in vitro adrenal gland response to adrenocorticotropic hormone stimulation in control rats at all ages and in trained rats at 170 days of age. The in vivo relationship of epinephrine and the pituitary adrenal system is suggested as a mechanism which could have caused this response. The relationship of secretion rates to plasma corticosterone concentrations indicated that extra-adrenal mechanisms, such as decreased turnover, were also responsible for the elevated plasma corticosterone levels observed in response to acute swimming.

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