FAILURE TO INHIBIT CORTICOTROPHIN SECRETION BY EXPERIMENTALLY INDUCED INCREASES IN CORTICOID LEVELS

1963 ◽  
Vol 44 (1) ◽  
pp. 36-46 ◽  
Author(s):  
P. G. Smelik
Keyword(s):  
Acute Stress ◽  
Plasma Corticosterone ◽  
Blood Levels ◽  
Endogenous Production ◽  
Anaesthetized Rats ◽  
Response To Stress ◽  
Adrenal Response ◽  
Physiological Values ◽  
Physiological Variations

ABSTRACT The present experiments were designed in order to investigate whether physiological elevations in corticoid blood levels would inhibit the pituitary-adrenal response to stress. Plasma corticosterone (11β,21-dihydroxypregn-4-ene-3,20-dione) levels and the in vitro corticoid production by excised adrenals were determined in anaesthetized rats, pretreated with corticosterone solutions injected intravenously or intramuscularly. Intravenous administration of small amounts of corticosterone induced a very high but transient peak in plasma corticosterone concentrations. Corticosterone infusion caused a constant increase in plasma corticosterone levels. Increases exceeding maximal physiological values did not prevent the adrenocortical activation produced by histamine or corticotrophin. The summation of exogenous (infused) and endogenous (produced) corticosterone in the plasma became incomplete with increasing levels. This summation was not due to an increasing inhibition of the endogenous production, but to a higher rate of disappearance from the blood. It is concluded that these data are not in agreement with the »variable set point control theory[00AP], and demonstrate that physiological variations in plasma corticoid concentration do not affect the acute stress-induced corticotrophin release.

EFFECTS OF PROLACTIN ON PITUITARY-ADRENAL FUNCTION IN INTACT AND OVARIECTOMIZED RATS

1978 ◽  
Vol 88 (4) ◽  
pp. 744-753 ◽  
Author(s):  
Silvia B. Vasquez ◽  
Julian I. Kitay
Keyword(s):  
Reductase Activity ◽  
Combined Treatment ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Response To Stress ◽  
Adrenal Response ◽  
Secretion Rates

ABSTRACT The influence of prolactin treatment (100 μg/100 g body wt. sc daily for 7 days) on plasma corticosterone levels, adrenal steroid production in vitro and in vivo and pituitary-adrenal responses to stress were studied in intact and castrated female rats. Prolactin enhanced plasma corticosterone levels and corticosterone production in vitro and in vivo in intact rats after stress. Differences were abolished with ACTH treatment. In contrast, prolactin administration to ovariectomized rats inhibited plasma corticosterone response to stress. Combined treatment with ACTH reversed these findings. A greater in vitro production of corticosterone by adrenal slices and adrenal homogenates associated with an effective inhibition of adrenal 5α-reductase activity were also observed. Secretion of DHB in adrenal venous blood was decreased as well, without changes in corticosterone or THB secretion rates. However, combined treatment with prolactin and ACTH produced greater increments in secretion rates of corticosterone than those obtained with prolactin alone. The data suggest that prolactin treatment to ovariectomized rats has a dual effect: a) adrenal responsiveness to ACTH is enhanced by its effects on adrenal 5α-reductase activity, and b) pituitary-adrenal response to stress is dampered by prolactin treatment. The effects of prolactin on adrenal 5α-reductase activity and corticosterone production in vitro were paralleled in vivo only after the exogenous administration of ACTH. The presence of the gonads apparently prevented the inhibitory effect of prolactin on ACTH secretion and in turn seemed to act synergistically with prolactin to facilitate pituitary-adrenal response to stress.

scholarly journals Loss of CREBRF Reduces Anxiety-like Behaviors and Circulating Glucocorticoids in Male and Female Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Krystle A Frahm ◽  
Akeem A Williams ◽  
Ashlee N Wood ◽  
Michael C Ewing ◽  
Polly E Mattila ◽  
...  
Keyword(s):  
Stress Responses ◽  
Acute Stress ◽  
Plasma Corticosterone ◽  
Affective States ◽  
Male And Female ◽  
Female Mice ◽  
Glucocorticoid Signaling ◽  
Plus Maze ◽  
The Impact

Abstract Glucocorticoid signaling controls many key biological functions ranging from stress responses to affective states. The putative transcriptional coregulator CREB3 regulatory factor (CREBRF) reduces glucocorticoid receptor levels in vitro, suggesting that CREBRF may impact behavioral and physiological outputs. In the present study, we examined adult male and female mice with global loss of CREBRF (CrebrfKO) for anxiety-like behaviors and circulating glucocorticoids in response to various acute stress conditions. Results demonstrate that both male and female CrebrfKO mice have preserved locomotor activity but reduced anxiety-like behaviors during the light–dark box and elevated plus maze. These behavioral phenotypes were associated with lower plasma corticosterone after restraint stress. Further studies using unhandled female mice also demonstrated a loss of the diurnal circulating corticosterone rhythm in CrebrfKO mice. These results suggest that CREBRF impacts anxiety-like behavior and circulating glucocorticoids in response to acute stressors and serves as a basis for future mechanistic studies to define the impact of CREBRF in glucocorticoid-associated behavioral and physiological responses.

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.

Stimulatory effect of caffeine on the hypothalamo-pituitary-adrenocortical axis in the rat

1989 ◽  
Vol 122 (2) ◽  
pp. 535-543 ◽  
Author(s):  
S. A. Nicholson
Keyword(s):  
Plasma Corticosterone ◽  
Corticotrophin Releasing Factor ◽  
Basal Release ◽  
Response To Stress ◽  
Corticosterone Response ◽  
Pharmacological Blockade ◽  
High Concentrations ◽  
Related Increase

ABSTRACT Intraperitoneal injection of caffeine (12·5–100 mg/kg) into rats caused a significant, dose-related increase in plasma corticosterone 2 h later, when the greatest response was measured. The corticosterone response to laparotomy stress or i.v. injection of ACTH(1–24) was unaffected by prior injection of caffeine. The response to stress or caffeine was unaffected by adrenal enucleation 28 days previously. In vitro, 10 mmol caffeine/l stimulated basal release of corticosterone from adrenal quarters and potentiated the response to a sub-maximal stimulatory concentration of cyclic AMP (cAMP). The drug had no effect on release stimulated by a sub-maximal concentration of ACTH(1–24). Release of ACTH from pituitary fragments incubated in vitro was stimulated in a dose-related manner by caffeine (0·01–10 mmol/l), and the responses to hypothalamic extract and sub-maximal concentrations of corticotrophin-releasing factor (CRF-41) or arginine vasopressin (AVP), but not cAMP, were significantly enhanced by 10 mmol caffeine/l. Release of immunoreactive CRF-41 (but not AVP) was significantly increased by caffeine (0·01–10 mmol/l) added to hypothalami incubated in vitro. The response to injection of caffeine in vivo was completely prevented by pharmacological blockade of endogenous CRF release. Taken together, these results show that caffeine at high concentrations can stimulate directly the release of the hormones of the hypothalamo-pituitary-adrenocortical axis in vitro, but the fact that these concentrations are unlikely to be reached after administration in vivo suggests that the effect of caffeine may be mediated centrally. Journal of Endocrinology (1989) 122, 535–543

EFFECT OF HYPOTHALAMIC LESIONS AND HYPOPHYSECTOMY ON CORTICOID PRODUCTION IN VITRO AND ON ADRENAL WEIGHT IN RATS

1961 ◽  
Vol 37 (2) ◽  
pp. 279-287 ◽  
Author(s):  
D. de Wied
Keyword(s):  
Adrenal Gland ◽  
Adrenal Weight ◽  
Weight Changes ◽  
Left Adrenal Gland ◽  
Hypophysectomized Rats ◽  
Response To Stress ◽  
Adrenal Response ◽  
The Right ◽  
Intact Rats

ABSTRACT Intact, sham-operated, hypophysectomized rats and rats bearing extensive lesions in the median eminence were stressed by ether anaesthesia. The pituitary-adrenal response to the stress was determined on the in vitro steroidogenesis by adrenal gland slices of the left gland and on adrenal weight changes in the left and right gland. The absence of compensatory adrenal hypertrophy which normally occurs following the removal of the left gland, was used as an index of the inhibition of the secretion of ACTH (corticotrophin) from the adenohypophysis in the lesioned rats. Following ether stress, corticoid production in vitro of the left adrenal gland rose considerably in intact rats. Adrenal response to stress of sham-operated animals was almost similar to that of intact rats at 4, 66 and 162 hours but significantly depressed at 18 hours following operation. Hypophysectomized and lesioned rats, however, failed to exhibit an increased steroidogenesis in vitro following ether stress at the four time intervals studied. Pitressin markedly stimulated corticoidogenesis of adrenals of lesioned rats at 18. 66 and 162 hours following the production of lesions. The weight of the left adrenal gland of lesioned and hypophysectomized rats decreased gradually during the period studied; that of the latter group decreased at a faster rate. Adrenal hypertrophy, usually observed some time after placement of a lesion, did not occur in the lesioned rats of the present experiments. Weight increase of the right adrenal removed one week following extirpation of the left gland, was similar in intact and sham-operated rats, whereas this compensatory adrenal hypertrophy was absent in hypophys-ectomized as well as in lesioned animals.

Effects of chronic hypothalamic lesions on diurnal and stress corticosteroid levels

1964 ◽  
Vol 206 (5) ◽  
pp. 1161-1164 ◽  
Author(s):  
Margaret A. Slusher
Keyword(s):  
Acute Stress ◽  
Indwelling Catheter ◽  
Blood Samples ◽  
Tuber Cinereum ◽  
Hypothalamic Lesions ◽  
Acute Response ◽  
Response To Stress ◽  
Adrenal Response ◽  
Arcuate Nuclei ◽  
Stimulation Of

The effect of chronic lesions on plasma corticosteroid levels has been assessed in an attempt to differentiate neuronal areas affecting diurnal corticosteroid rise from those involved in acute response to stress. In unanesthetized, unrestrained rats blood samples were collected through a chronic indwelling catheter on each of four experimental days at 9 and 10 am and 5 pm with or without addition of a stress applied at 9:45 am. Anterior hypothalamic lesions bilaterally destroying the periventricular zone and arcuate nuclei were associated with inhibition of the normal 5 pm rise but with normal rise in plasma corticosteroid levels in response to sound or to a 1-min electrical stimulation of the posterior diencephalon. Posterior tuber cinereum lesions were associated with normal 5 pm rise but with inhibition of response to sound. Response to ether stress was unaffected by any lesion. Thus the integrity of anterior hypothalamic areas appears essential for normal diurnal rise in plasma corticosteroid levels while more posterior areas are involved in mediation of pituitary-adrenal response to acute stress of sound.

scholarly journals Colitis induces CRF expression in hypothalamic magnocellular neurons and blunts CRF gene response to stress in rats

2001 ◽  
Vol 281 (5) ◽  
pp. G1203-G1213 ◽  
Author(s):  
Adelheid E. Kresse ◽  
Mulugeta Million ◽  
Esteban Saperas ◽  
Yvette Taché
Keyword(s):  
Acute Stress ◽  
Oligonucleotide Probe ◽  
Plasma Corticosterone ◽  
Gene Synthesis ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Gene Response ◽  
Response To Stress ◽  
Supraoptic Neurons

We investigated hypothalamic neuronal corticotropin-releasing factor (CRF) gene expression changes in response to visceral inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNB) and acute stress. Seven days after TNB, rats were subjected to water-avoidance stress (WAS) or restraint for 30 min and euthanized. Hypothalamic CRF primary transcripts (heteronuclear RNA, hnRNA) and CRF and arginine vasopressin (AVP) mRNAs were assessed by in situ hybridization. Antisense 35S-labeled cRNA probes against CRF mRNA intronic and exonic sequences and an oligonucleotide probe against the AVP mRNA were used. TNB induced macroscopic lesions and a fivefold elevation in myeloperoxidase activity in the colon. Colitis increased CRF hnRNA and mRNA signals in the magnocellular part of the paraventricular nucleus of the hypothalamus (PVN) and supraoptic neurons, whereas AVP mRNA was not altered. Colitis did not modify CRF hnRNA signal in the parvocellular part of the PVN (pPVN), plasma corticosterone, and serum osmolarity levels. However, CRF hnRNA expression in the pPVN and the rise in corticosterone and defecation induced by WAS or restraint were blunted in colitic rats. These data show that colitis upregulates CRF gene synthesis in magnocellular hypothalamic neurons but dampens CRF gene transcription in the pPVN and plasma corticosterone responses to environmental acute stressors.

In Vitro Clot Lysis as a Potential Indicator of Thrombus Resistance to Fibrinolysis – Study in Healthy Subjects and Correlation with Blood Fibrinolytic Parameters

1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro
Keyword(s):  
Plasminogen Activator ◽  
Clot Lysis ◽  
Individual Response ◽  
Plasminogen Activator Inhibitor 1 ◽  
Autologous Plasma ◽  
Wide Range ◽  
Blood Clots ◽  
Physiological Variations ◽  
Pai 1

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo
Keyword(s):  
Thyroid Function Test ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Function Test ◽  
Before And After ◽  
Adrenal Response ◽  
Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

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