Elevated corticosterone and inhibition of ACTH responses to CRH and ether in the neonatal rat: effect of hypoxia from birth

2003 ◽  
Vol 285 (5) ◽  
pp. R1224-R1230 ◽  
Author(s):  
Hershel Raff ◽  
Lauren Jacobson ◽  
William E. Cullinan
Keyword(s):  
Thyroid Function ◽  
Neonatal Morbidity ◽  
Neonatal Rat ◽  
Biochemical Mechanism ◽  
Neonatal Rats ◽  
Plasma Acth ◽  
Pomc Mrna ◽  
Adrenal Steroidogenesis ◽  
Before And After ◽  
Pituitary Adrenal Axis

Hypoxia is a common cause of neonatal morbidity and mortality. We have previously demonstrated a dramatic ACTH-independent activation of adrenal steroidogenesis in hypoxic neonatal rats, leading to increases in circulating corticosterone levels. The purpose of the present study was to determine if this ACTH-independent increase in corticosterone inhibits the ACTH response to acute stimuli. Neonatal rats were exposed to normoxia (control) or hypoxia from birth to 5 or 7 days of age. At the end of the exposure, plasma ACTH and corticosterone were measured before and after either ether vapors were administered for 3 min or CRH (10 μg/kg) was given intraperitoneally. Thyroid function, pituitary pro-opiomelanocortin (POMC) mRNA and ACTH content, and hypothalamic corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), and AVP mRNA were also assessed. Hypoxia led to a significant increase in corticosterone without a large increase in ACTH, confirming previous studies. The ACTH responses to ether or CRH administration were almost completely inhibited in hypoxic pups. Hypoxia did not affect the established regulators of the neonatal hypothalamic-pituitary-adrenal axis, including pituitary POMC or ACTH content, hypothalamic CRH, NPY, or AVP mRNA (parvo- or magnocellular), or thyroid function. We conclude that hypoxia from birth to 5 or 7 days of age leads to an attenuated ACTH response to acute stimuli, most likely due to glucocorticoid negative feedback. The neural and biochemical mechanism of this effect has yet to be elucidated.

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.

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.

SOMATOTROPHIC AND CORTICOTROPHIC FUNCTIONS IN PRIMARY HYPOTHYROIDISM BEFORE AND AFTER THYROXINE TREATMENT

1973 ◽  
Vol 74 (3) ◽  
pp. 483-491 ◽  
Author(s):  
M. Minozzi ◽  
M. Faggiano ◽  
G. Lombardi ◽  
C. Carella ◽  
T. Criscuolo ◽  
...  
Keyword(s):  
Primary Hypothyroidism ◽  
Pituitary Function ◽  
Plasma Acth ◽  
Arginine Infusion ◽  
Hypothalamic Pituitary Adrenal ◽  
Thyroxine Treatment ◽  
Before And After ◽  
Pituitary Adrenal Axis ◽  
Different Levels ◽  
Multiple Interference

ABSTRACT In 12 patients with primary hypothyroidism the somatotrophic and corticotrophic functions were evaluated before and after thyroxine treatment. The results confirm a significant decrease, reversible by treatment, of plasma HGH responses to insulin-induced hypoglycaemia and to arginine infusion. Moreover, the results indicate that the impairment of the hypothalamic-pituitary function may also involve the response of plasma ACTH after provocative tests (insulin-induced hypoglycaemia and metyrapone). It must be stressed that the impairment of the corticotrophic function can be revealed only when the responses to provocative tests are evaluated by a direct assay of plasma ACTH and not by plasma corticosteroid modifications. These different responses may account for the conflicting results obtained by other investigators and may be justified by the multiple interference of the thyroid deficiency with the hypothalamic-pituitary-adrenal axis at different levels.

scholarly journals Glucocorticoid feedback control of corticotropin in the hypoxic neonatal rat

2007 ◽  
Vol 192 (2) ◽  
pp. 453-458 ◽  
Author(s):  
Hershel Raff ◽  
Lauren Jacobson
Keyword(s):  
Gene Expression ◽  
Anterior Pituitary ◽  
Low Dose ◽  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Neonatal Rats ◽  
Plasma Acth ◽  
Basal Plasma ◽  
Old Rats ◽  
Per Se

The objective of this study was to determine the effects of manipulating glucocorticoid negative feedback on acute ACTH and corticosterone responses to corticotropin-releasing hormone (CRH) injection in 7-day-old rats exposed to normoxia or hypoxia from birth. Chemical adrenalectomy was achieved with aminoglutethimide, and glucocorticoids were replaced with a low dose of dexamethasone. Hypoxia per se increased basal plasma corticosterone and attenuated the plasma ACTH response to CRH. Aminoglutethimide per se decreased plasma corticosterone and strongly increased basal plasma ACTH and anterior pituitary POMC gene expression. Dexamethasone partially attenuated elevations in basal plasma ACTH due to aminoglutethimide in both normoxic and hypoxic pups, but inhibited anterior pituitary POMC expression and CRH-induced plasma ACTH only in hypoxic pups. Despite this inhibition, hypoxic pups treated with both dexamethasone and aminoglutethimide still exhibited a significant CRH-induced increment in plasma ACTH, which was lacking in hypoxic pups not treated with either dexamethasone or aminoglutethimide. We conclude that ACTH responses to acute stimuli in hypoxic neonatal rats are prevented by ACTH-independent increases in corticosterone, rather than by intrinsic hypothalamic–pituitary hypoactivity.

The effects of recombinant human interleukin (IL)-1α, IL-1β or IL-6 on hypothalamo-pituitary-adrenal axis activation

1992 ◽  
Vol 133 (3) ◽  
pp. 349-355 ◽  
Author(s):  
M. S. Harbuz ◽  
A. Stephanou ◽  
N. Sarlis ◽  
S. L. Lightman
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Anterior Pituitary ◽  
Plasma Acth ◽  
Adrenal Axis ◽  
Corticotrophin Releasing Factor ◽  
Pomc Mrna ◽  
Pomc Gene ◽  
Pituitary Adrenal Axis ◽  
Time Point

ABSTRACT We have investigated the effects of recombinant human interleukin (IL)-1α, IL-1β and IL-6 on the activation of the hypothalamo-pituitary-adrenal axis. We have determined the effects of a single i.p. injection of cytokine on circulating ACTH and corticosterone levels, corticotrophin-releasing factor (CRF) mRNA in the parvocellular cells of the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary at both 4 h and 24 h after injection. IL-1α had no effect on any of the parameters measured at either time-point. In contrast, IL-1β increased CRF mRNA in the parvocellular paraventricular nucleus and POMC mRNA in the anterior pituitary 4 h after injection. Plasma ACTH and corticosterone were increased at 4 h and circulating ACTH was still increased at 24 h after treatment with IL-1β. IL-6 had no effect on message levels but did increase circulating ACTH and corticosterone levels both 4 h and 24 h after injection. The mechanism responsible for the increase in circulating ACTH after IL-6 injection is unclear but would appear to be different from that which is activated by IL-1β which also results in increased CRF and POMC gene expression. Journal of Endocrinology (1992) 133, 349–355

Aerodynamic and Acoustic Voice Measures Before and After an Acute Public Speaking Stressor

2020 ◽  
Vol 63 (10) ◽  
pp. 3311-3325
Author(s):  
Brittany L. Perrine ◽  
Ronald C. Scherer
Keyword(s):  
Fundamental Frequency ◽  
Salivary Cortisol ◽  
Public Speaking ◽  
Stress System ◽  
Before And After ◽  
Subglottal Pressure ◽  
Response To Stress ◽  
System Activation ◽  
Speaking Fundamental Frequency ◽  
Pituitary Adrenal Axis

Purpose The goal of this study was to determine if differences in stress system activation lead to changes in speaking fundamental frequency, average oral airflow, and estimated subglottal pressure before and after an acute, psychosocial stressor. Method Eighteen vocally healthy adult females experienced the Trier Social Stress Test (TSST) to activate the hypothalamic–pituitary–adrenal axis. The TSST includes public speaking and performing mental arithmetic in front of an audience. At seven time points, three before the stressor and four after the stressor, the participants produced /pa/ repetitions, read the Rainbow Passage, and provided a saliva sample. Measures included (a) salivary cortisol level, (b) oral airflow, (c) estimated subglottal pressure, and (d) speaking fundamental frequency from the second sentence of the Rainbow Passage. Results Ten of the 18 participants experienced a hypothalamic–pituitary–adrenal axis response to stress as indicated by a 2.5-nmol/L increase in salivary cortisol from before the TSST to after the TSST. Those who experienced a response to stress had a significantly higher speaking fundamental frequency before and immediately after the stressor than later after the stressor. No other variable varied significantly due to the stressor. Conclusions This study suggests that the idiosyncratic and inconsistent voice changes reported in the literature may be explained by differences in stress system activation. In addition, laryngeal aerodynamic measures appear resilient to changes due to acute stress. Further work is needed to examine the influence of other stress systems and if these findings hold for dysphonic individuals.

scholarly journals Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats

2021 ◽  
Vol 22 (12) ◽  
pp. 6306
Author(s):  
Jiann-Horng Yeh ◽  
Kuo-Ching Wang ◽  
Asuka Kaizaki ◽  
Jonathan W. Lee ◽  
Han-Chi Wei ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
White Matter ◽  
Brain Inflammation ◽  
White Matter Injury ◽  
Neonatal Rat ◽  
Mitochondrial Activity ◽  
Neonatal Rats ◽  
Activated Microglia ◽  
Brain White Matter ◽  
Performance Reduction

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.

Thyroid function before and after four-week light treatment in winter depressives and controls

1993 ◽  
Vol 18 (5-6) ◽  
pp. 437-443 ◽  
Author(s):  
Mark S. Bauer ◽  
James Kurtz ◽  
Andrew Winokur ◽  
Jennifer Phillips ◽  
Lisa B. Rubin ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Light Treatment ◽  
Before And After

EFFECT OF LITHIUM ON THYROID FUNCTION IN MAN

1972 ◽  
Vol 70 (2) ◽  
pp. 266-272 ◽  
Author(s):  
J. H. Lazarus ◽  
E. H. Bennie
Keyword(s):  
Thyroid Function ◽  
Lithium Carbonate ◽  
Lithium Therapy ◽  
Thyroid Status ◽  
Prospective Survey ◽  
Significant Fall ◽  
Concentrating Mechanism ◽  
Before And After

ABSTRACT Thyroid function was assessed in a prospective survey of 13 manicdepressive patients before and after 3 months on lithium carbonate and in a further 12 patients who had received lithium for 20 months. There was a significant increase in thyroid size as measured by quantitative scintiscanning in 8 patients in the first group. One male in the second group had a goitre. There was a rise in plasma TSH in the first group and a significant fall in saliva to plasma iodide. It is suggested that pathogenesis of lithium induced goitre is related to a disturbance in the iodide concentrating mechanism. Thyroid status should be evaluated in patients who are suitable for lithium therapy.

Role of hypothalamic inputs in maintaining pituitary-adrenal responsiveness in repeated restraint

2003 ◽  
Vol 285 (5) ◽  
pp. E1110-E1117 ◽  
Author(s):  
D. Zelena ◽  
Z. Mergl ◽  
A. Földes ◽  
K. J. Kovács ◽  
Z. Tóth ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Stress Responses ◽  
Mrna Level ◽  
Hormonal Changes ◽  
Mediobasal Hypothalamus ◽  
Hormonal Responses ◽  
Pomc Mrna ◽  
Paraventricular Nucleus Of Hypothalamus ◽  
Pituitary Adrenal Axis

The role of hypothalamic structures in the regulation of chronic stress responses was studied by lesioning the mediobasal hypothalamus or the paraventricular nucleus of hypothalamus (PVH). Rats were acutely (60 min) and/or repeatedly (for 7 days) restrained. In controls, a single restraint elevated the plasma adrenocorticotropin (ACTH), corticosterone, and prolactin levels. Repeated restraint produced all signs of chronic stress, including decreased body and thymus weights, increased adrenal weight, basal corticosterone levels, and proopiomelanocortin (POMC) mRNA expression in the anterior pituitary. Some adaptation to repeated restraint of the ACTH response, but not of other hormonal responses, was seen. Lesioning of the mediobasal hypothalamus abolished the hormonal response and POMC mRNA activation to acute and/or repeated restraint, suggesting that the hypothalamo-pituitary-adrenal axis activation during repeated restraint is centrally driven. PVH lesion inhibited the ACTH and corticosterone rise to the first restraint by ∼50%. In repeatedly restrained rats with PVH lesion, the ACTH response to the last restraint was reduced almost to basal control levels, and the elevation of POMC mRNA level was prevented. PVH seems to be important for the repeated restraint-induced ACTH and POMC mRNA stimulation, but it appears to partially mediate other restraint-induced hormonal changes.

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