Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function

2000 ◽  
Vol 279 (5) ◽  
pp. R1841-R1848 ◽  
Author(s):  
Zheng F. Ba ◽  
Ping Wang ◽  
Douglas J. Koo ◽  
Mian Zhou ◽  
William G. Cioffi ◽  
...  
Keyword(s):  
Adrenal Function ◽  
Male Rats ◽  
Ringer Lactate ◽  
Acth Stimulation ◽  
Camp Content ◽  
Morphological Alterations ◽  
Shed Blood ◽  
Corticosterone Response ◽  
Corticosterone Release ◽  
Adrenal Corticosterone

Although the testosterone receptor antagonist flutamide restores the depressed immune function in males after trauma and hemorrhage, it remains unknown whether this agent has any salutary effects on adrenal function. To study this, male rats underwent laparotomy and were bled to and maintained at a blood pressure of 40 mmHg until 40% of the shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated and flutamide (25 mg/kg body wt) was administered subcutaneously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone, as well as adrenal corticosterone and cAMP were measured 20 h after resuscitation. In additional animals, ACTH was administered and ACTH-induced corticosterone release and adrenal cAMP were determined. The results indicate that adrenal contents of corticosterone and cAMP were significantly decreased and morphology was altered after hemorrhage. Administration of flutamide improved corticosterone content, restored cAMP content, and attenuated adrenal morphological alterations. Flutamide also improved the diminished ACTH-induced corticosterone release and adrenal cAMP response at 20 h after hemorrhage and resuscitation. Furthermore, the diminished corticosterone response to ACTH stimulation in the isolated adrenal preparation was improved with flutamide. These results suggest that flutamide is a useful adjunct for improving adrenal function in males following trauma and hemorrhage.

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males

1997 ◽  
Vol 273 (6) ◽  
pp. H2919-H2925 ◽  
Author(s):  
Dierk E. Remmers ◽  
Ping Wang ◽  
William G. Cioffi ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Cardiac Output ◽  
Blood Volume ◽  
Maximum Velocity ◽  
Left Ventricular ◽  
Male Rats ◽  
Microvascular Blood Flow ◽  
Receptor Blockade ◽  
Ringer Lactate ◽  
Ventricular Performance ◽  
Shed Blood

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Enhancement of corticosterone release by repeated injections of ACTH in the dexamethasone pre-treated rat

1983 ◽  
Vol 102 (4) ◽  
pp. 583-588 ◽  
Author(s):  
Noboru Murakami ◽  
Kiyohisa Takahashi
Keyword(s):  
Body Weight ◽  
Adrenal Gland ◽  
Adrenocorticotrophic Hormone ◽  
Blood Samples ◽  
Pulsatile Secretion ◽  
The Third ◽  
Daily Variations ◽  
Corticosterone Response ◽  
Corticosterone Release ◽  
Adrenal Corticosterone

Abstract. To examine the possibility that pulsatile secretion of adrenocorticotrophic hormone (ACTH) enhances the responsiveness of the adrenal, the blood corticosterone response to repeated injections of ACTH was determined in the dexamethasone-nembutal pre-treated rat. Treatment with dexamethasone (100 μg/100 g body weight) at 13.00 h for 2 days decreased corticosterone levels and completely abolished these daily variations in both the blood and adrenal. Under these conditions, four or five successive iv injections of 0.2 or 2 mIU ACTH were given at ½ or 1 h intervals. Blood samples were taken immediately before and at frequent intervals after injection. A significant increase of blood corticosterone levels was observed 10 min after the second injection of 0.2 mIU ACTH. Further increases in blood corticosterone levels were observed after the subsequent injections. In addition, repeated injections of 2 mIU ACTH augmented the responsiveness of the adrenal to ACTH. The second or the third injections of 2 mIU ACTH produced a greater increase in adrenal corticosterone content than did the first ACTH injection. These results suggest that when ACTH acts on the adrenal gland in a pulsatile fashion, the steroidogenic response of the adrenal to ACTH increases markedly.

Inhibitory effects of gossypol on adrenal function

1991 ◽  
Vol 124 (6) ◽  
pp. 672-678 ◽  
Author(s):  
Yan-Wan Wu ◽  
Constance L. Chik ◽  
Barry D. Albertson ◽  
W. Marston Linehan ◽  
Richard A. Knazek
Keyword(s):  
Adrenal Function ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Acth Stimulation ◽  
Adrenal Steroidogenesis ◽  
Cortisol Responses ◽  
Corticosterone Response ◽  
High Doses ◽  
Dose Dependent

Abstract. Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3β-hydroxysteroid dehydrogenase Δ5-Δ4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.

EFFECTS OF NORETHANDROLONE ON CORTISONE-INDUCED PITUITARY-ADRENAL SUPPRESSION IN THE RAT

1966 ◽  
Vol 52 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Julian I. Kitay ◽  
M. D. Coyne
Keyword(s):  
Combined Therapy ◽  
Test Dose ◽  
Hepatic Metabolism ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Concomitant Treatment ◽  
Response To Stress ◽  
Corticosterone Response ◽  
Adrenal Corticosterone

ABSTRACT Norethandrolone administered to castrated male rats stimulated adrenal corticosterone production evaluated in vitro and increased pituitary content of corticotrophin (ACTH). Hepatic metabolism of corticosterone in vitro was unchanged. Concomitant treatment with norethandrolone and cortisone resulted in significantly greater adrenal corticosterone production in vitro compared to that obtained after cortisone treatment alone. Combined therapy also enhanced the plasma corticosterone response to a test dose of ACTH. No improvement was noted in the response to stress, offering no substantiation to the hypothesis that norethandrolone is of value in overcoming cortisone-induced depression of pituitary ACTH release.

scholarly journals The transformation of hormonal stress responses throughout puberty and adolescence

2011 ◽  
Vol 210 (3) ◽  
pp. 391-398 ◽  
Author(s):  
Allison R Foilb ◽  
Patina Lui ◽  
Russell D Romeo
Keyword(s):  
Stress Response ◽  
Adolescent Development ◽  
Stress Responses ◽  
Stress Reactivity ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Before And After ◽  
Corticosterone Response ◽  
Acute Stressor ◽  
Adrenal Corticosterone

Prepubertal rats display heightened hormonal stress reactivity compared with adults in that levels of ACTH and corticosterone take twice as long (i.e. 40–60 min) to return to baseline following an acute stressor. Despite this substantial change in stress responsiveness, and the critical nature of the adolescence period of development, the maturation of the hormonal stress response from the time of pubertal onset to adulthood has not been thoroughly investigated. To examine this, we measured ACTH, corticosterone, and testosterone in 30-, 40-, 50-, 60-, and 70-day-old (i.e. spanning pubertal and adolescent development) male rats before and after a 30 min session of restraint stress. We found that the adult-like ACTH stress response develops between 50 and 60 days of age, while the corticosterone response changes between 30 and 40 days of age. We also found that adrenal corticosterone concentrations paralleled the plasma corticosterone response following restraint, suggesting that stress-induced adrenal corticosterone synthesis decreases during adolescent development and may, at least in part, contribute to the differential stress response observed before and after puberty. Finally, stress leads to increases in testosterone secretion, but only after 50 days of age. Collectively, these results indicate that shifts in hormonal stress responses occur throughout adolescent maturation and that these responses show distinct developmental profiles.

scholarly journals Corticosterone increase inhibits stress-induced gastric erosions in rats

1998 ◽  
Vol 274 (6) ◽  
pp. G1024-G1030 ◽  
Author(s):  
L. P. Filaretova ◽  
A. A. Filaretov ◽  
G. B. Makara
Keyword(s):  
Glucocorticoid Receptors ◽  
Rabbit Antiserum ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Gastric Erosions ◽  
Response To Stress ◽  
Corticosterone Response ◽  
Corticosterone Release ◽  
Corticosteroid Secretion

The role of glucocorticoids released in response to stress in the pathogenesis of stress-induced gastric erosions has been reevaluated. Gastric erosions elicited in male rats by 3-h cold-restraint or water-restraint stresses were studied after acute reduction of corticosterone release or occupation of glucocorticoid receptors by the antagonist RU-38486 during stress. Stress-induced corticosterone production was reduced by creating a lesion on the hypothalamic paraventricular nucleus (PVN) 4 days before stress as well as by pretreatment with a rabbit antiserum to adrenocorticotropin (ACTH) 30 min before stress. RU-38486 (10 mg/kg po) was administered 20 min before and 60 min after the onset of stress. Corticosterone for replacement was injected 15 min before the onset of stress to mimic stress-induced corticosterone response. Plasma corticosterone levels were measured by fluorometry or RIA. Gastric erosions were quantitated by measuring the area of damage. Four days after PVN lesion, stress-induced corticosterone release was decreased and gastric erosions were increased. Injecting corticosterone significantly attenuated the effect of PVN lesion on gastric erosions. The ACTH antiserum inhibited corticosteroid secretion in response to stress and markedly increased gastric erosions. The administration of the glucocorticoid/progesterone antagonist RU-38486 significantly potentiated the formation of stress-induced gastric erosions. These observations support the suggestion that glucocorticoids released during stress have a gastroprotective action rather than an ulcerogenic effect as was generally accepted.

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.

Serotoninergic regulation of corticosterone secretion in domestic fowl

1987 ◽  
Vol 113 (2) ◽  
pp. 159-165 ◽  
Author(s):  
A. Cheung ◽  
T. R. Hall ◽  
S. Harvey
Keyword(s):  
Domestic Fowl ◽  
Serotonin Receptor ◽  
Plasma Concentrations ◽  
Adrenocortical Function ◽  
Serotoninergic System ◽  
Acth Stimulation ◽  
Corticosterone Secretion ◽  
Corticosterone Release ◽  
Adrenal Corticosterone

ABSTRACT The effects of serotoninergic drugs on adrenocortical function in domestic fowl were examined. Administration of the serotonin receptor agonist 2-(1-piperazinyl)quinoline maleate (quipazine), an inhibitor of serotonin metabolism, N-methyl-N-2-propynylbenzylamine HCl (pargyline), as well as serotonin itself, all increased plasma concentrations of corticosterone. The maximum responses to serotonin and quipazine occurred 1 h after treatment. The quipazine-stimulated response was partly prevented by the serotonin antagonist cyproheptadine. Cockerels pretreated with dexamethasone, a synthetic steroid known to inhibit pituitary ACTH release, showed attenuated responses to subsequent quipazine, pargyline or serotonin injection. Serotonin, quipazine and cyproheptadine did not affect corticosterone release directly from the adrenal gland incubated in vitro, nor did they affect adrenal responsiveness to ACTH stimulation. The neurotoxin 5,6-dihydroxytryptamine injected into day-old chicks decreased plasma concentrations of corticosterone for up to 7 days after treatment, with corresponding decreases in the hypothalamic concentration of serotonin, but not dopamine or noradrenaline concentrations. These results show that adrenal corticosterone secretion is regulated by a central serotoninergic system, probably acting on the hypothalamo-pituitary-adrenal axis. J. Endocr. (1987) 113,159–165

DER EINFLUSS VON RESERPIN AUF DIE ANTITHYREOIDALE WIRKUNG VON KALIUMPERCHLORAT

1962 ◽  
Vol 39 (3) ◽  
pp. 423-430
Author(s):  
H. L. Krüskemper ◽  
F. J. Kessler ◽  
E. Steinkrüger
Keyword(s):  
Thyroid Gland ◽  
Male Rats ◽  
Normal Male ◽  
Tissue Respiration ◽  
List Type ◽  
Morphological Alterations ◽  
Hormone Synthesis ◽  
Stimulation Of

ABSTRACT 1. Reserpine does not inhibit the tissue respiration of liver in normal male rats (in vitro). 2. The decrease of tissue respiration of the liver with simultaneous morphological stimulation of the thyroid gland after long administration of reserpine is due to a minute inhibition of the hormone synthesis in the thyroid gland. 3. The morphological alterations of the thyroid in experimental hypothyroidism due to perchlorate can not be prevented with reserpine.

Adrenal and gonadal function in hypothyroid adult male rats

1997 ◽  
Vol 152 (1) ◽  
pp. 147-154 ◽  
Author(s):  
A Tohei ◽  
M Akai ◽  
T Tomabechi ◽  
M Mamada ◽  
K Taya
Keyword(s):  
Adult Male ◽  
Functional Relationship ◽  
Plasma Concentrations ◽  
Gonadal Hormones ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Male Rats ◽  
Plasma Acth ◽  
Corticosterone Release ◽  
Acth Release

Abstract The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouracil-treated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH. Journal of Endocrinology (1997) 152, 147–154

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