scholarly journals Impact of hydrocortisone and of CRH infusion on the hypothalamus-pituitary-adrenocortical axis of septic male mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Arno Téblick ◽  
Lauren De Bruyn ◽  
Tim Van Oudenhove ◽  
Sarah Vander Perre ◽  
Lies Pauwels ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Ex Vivo ◽  
High Plasma ◽  
Plasma Acth ◽  
Markers Of Inflammation ◽  
Equimolar Dose ◽  
And Function ◽  
Stimulation Of

Abstract Purpose Sepsis is hallmarked by high plasma cortisol/corticosterone (CORT), low adrenocorticotropic hormone (ACTH) and high pro-opiomelanocortin (POMC). While corticotropin-releasing hormone-(CRH) and arginine-vasopressin-(AVP) driven pituitary POMC expression remains active, POMC processing into ACTH becomes impaired. Low ACTH is accompanied by loss of adrenocortical structure, although steroidogenic enzymes remain expressed. We hypothesized that treatment of sepsis with hydrocortisone (HC) aggravates this phenotype whereas CRH infusion safeguards ACTH-driven adrenocortical structure. Methods In a fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis, we compared the effects of HC and CRH infusion with placebo, on plasma ACTH, POMC and CORT and on markers of hypothalamic CRH and AVP signaling and pituitary POMC processing, and on the adrenocortical structure and markers of steroidogenesis. In adrenal explants, we studied the steroidogenic capacity of POMC. Results During sepsis, HC further suppressed plasma ACTH, but not POMC, predominantly by suppressing sepsis-activated CRH/AVP-signaling pathways. In contrast, in CRH-treated sepsis, plasma ACTH was normalized following restoration of pituitary POMC processing. The sepsis-induced rise in markers of adrenocortical steroidogenesis was unaltered by CRH and suppressed partially by HC which also increased adrenal markers of inflammation. Ex vivo stimulation of adrenal explants with POMC increased CORT as effectively as an equimolar dose of ACTH. Conclusions Treatment of sepsis with HC impaired integrity and function of the HPA axis at the level of the pituitary and the adrenal cortex while CRH restored pituitary POMC processing without affecting the adrenal cortex. Sepsis-induced high circulating POMC may be responsible for ongoing adrenocortical steroidogenesis despite low ACTH.

scholarly journals Endocrine and Electrolyte Balances during Periovulatory Period in Cycling Mares

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 520 ◽  
Author(s):  
Katiuska Satué ◽  
Esterina Fazio ◽  
Ana Muñoz ◽  
Pietro Medica
Keyword(s):  
Estrous Cycle ◽  
Hpa Axis ◽  
Adrenocorticotropic Hormone ◽  
Venous Blood ◽  
Competitive Elisa ◽  
Direct Relation ◽  
Plasma Acth ◽  
Blood Samples ◽  
Hypothalamic Pituitary Adrenal ◽  
Stimulation Of

In cycling females, the periovulatory period is characterized by stimulation of the hypothalamic pituitary adrenal (HPA) axis. The aim of present study was to analyze the pattern and interrelationships among adrenocorticotropic hormone (ACTH), cortisol (CORT), aldosterone (ALD) and electrolytes (sodium—Na+, potassium—K+ and chloride—Cl−) during periovulatory period in cycling mares. Venous blood samples were obtained daily from a total of 23 Purebred Spanish broodmares, aged 7.09 ± 2.5 years, from day −5 to day +5 of estrous cycle, considering day 0, the day of ovulation. Plasma ACTH was measured by a fluorescent immunoassay kit, serum CORT and ALD by means of a competitive ELISA immunoassay, and plasma Na+, K+ and Cl− were quantified by an analyzer with selective electrodes for the three ions. ACTH showed higher concentrations at day 0 compared to days −5 to −1 and +1 to +3 (p < 0.05). CORT showed higher concentrations at day 0 compared to days −5 to −2 and +1 to +5 (p < 0.05). ALD showed higher concentrations at day 0 compared to days −5 to −2 (p < 0.05) and +2 (p < 0.05). Na+ and Cl− showed higher concentrations at day 0, compared to day −5 and +5. K+ showed lower concentrations at day 0 compared to day +1 (p < 0.05). The significant correlations obtained between ACTH and CORT (r = 0.20) and between ACTH and ALD (r = 0.32) suggest that although ACTH may have an effect both on CORT and ALD, there are other very important determinants that could be considered. Hence, it is possible to presume that the pituitary adrenocortical response and ALD may be involved in the ovulatory mechanisms without a direct relation with electrolyte pattern.

ACTH and cortisol responses to hypotension in fetal sheep after a prior CRF injection

1992 ◽  
Vol 262 (3) ◽  
pp. E325-E329
Author(s):  
D. R. Kerr ◽  
M. I. Castro ◽  
N. K. Valego ◽  
N. M. Rawashdeh ◽  
J. C. Rose
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Feedback Effects ◽  
Maximal Stimulation ◽  
Endogenous Cortisol ◽  
Before And After ◽  
Cortisol Responses ◽  
Releasing Factors ◽  
Stimulation Of

To determine whether an ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to hypotension and whether the effect of any interactions between these stimuli changes across gestation, we studied chronically cannulated fetal lambs of 103-113 ("immature") and 133-139 days gestation ("mature"). Experimental groups received 500 ng/kg oCRF injections and 6 h later had arterial pressure reduced 20% for 10 min with nitroprusside. Blood samples were obtained before and after each manipulation. Controls received vehicle instead of oCRF. The oCRF increased plasma cortisol levels from 2.1 +/- 0.4 to 14.2 +/- 4.7 (SE) ng/ml in immature and 44.9 +/- 2.2 to 102.8 +/- 15 ng/ml in mature animals. In mature fetuses the oCRF did not alter plasma ACTH and cortisol increases due to hypotension. In immature animals ACTH increases were normal but cortisol increases were eliminated. This suggests that the CRF caused maximal stimulation of the adrenal gland. In older fetuses, it appears that the action of ACTH-releasing factors, secreted in response to arterial hypotension, can overcome the negative feedback effects of elevations in endogenous cortisol.

Are fetal adrenocorticotropic hormone and renin secretion suppressed by maternal cortisol secretion?

1988 ◽  
Vol 255 (3) ◽  
pp. R412-R417 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Maternal Plasma ◽  
Renin Secretion ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Adrenal Secretion

Previous studies from this laboratory have demonstrated that intravenous infusions of hydrocortisone (cortisol) into fetal sheep at rates that produce plasma concentrations achieved during fetal stress inhibit fetal adrenocorticotropic hormone (ACTH) and renin secretion. The present study was designed to test for inhibition of fetal renin and ACTH after maternal adrenal secretion of cortisol. ACTH-(1-24) or saline infusion into 12 pregnant ewes (120-132 days gestation) at rates of 0, 1, 5, or 20 ng ACTH.kg-1.min-1 for 5 h produced dose-related increases in maternal plasma ACTH and cortisol concentrations and fetal plasma cortisol concentration. In the 20-ng.kg-1.min-1 group, increases in fetal plasma cortisol of 8.0 ng/ml (to 24.3 +/- 3.7 ng/ml) did not suppress basal fetal plasma renin activity. One hour after the end of the maternal vehicle or ACTH infusion, fetal ACTH secretion was stimulated by fetal intravenous infusion of sodium nitroprusside. In the 0-, 1-, and 5-ng.kg-1.min-1 groups, fetal ACTH responses to nitroprusside were suppressed in animals infused with ACTH. Together, these results indicate that the maternal adrenal secretion of cortisol inhibits stimulated secretion of ACTH but not renin in 120- to 132-day-gestation fetal sheep.

scholarly journals Regulation of maternal ACTH in ovine pregnancy: does progesterone play a role?

2008 ◽  
Vol 295 (4) ◽  
pp. E913-E920 ◽  
Author(s):  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Plasma Protein ◽  
Plasma Volume ◽  
Plasma Proteins ◽  
Plasma Cortisol ◽  
Protein Concentration ◽  
Adrenocorticotropic Hormone ◽  
Mineralocorticoid Receptors ◽  
Plasma Acth ◽  
Plasma Protein Concentration

Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg·kg−1·day−1 or 0.5 mg·kg−1·day−1 cortisol. In both studies, aldosterone was infused at 3 μg·kg−1·day−1. In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg·kg−1·day−1, and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg·kg−1·day−1. In adrenalectomized ewes chronically replaced to 0.35 mg·kg−1·day−1 cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg·kg−1·day−1 cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg·kg−1·day−1 were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.

Evidence for reset of regulated cortisol in pregnancy: studies in adrenalectomized ewes

1998 ◽  
Vol 274 (1) ◽  
pp. R145-R151 ◽  
Author(s):  
Maureen Keller-Wood
Keyword(s):  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Cortisol Concentration ◽  
Plasma Acth ◽  
Basal Cortisol ◽  
Acth Concentration ◽  
In Pregnancy

These studies test the hypothesis that the increased adrenocorticotropic hormone (ACTH) and cortisol in pregnancy reflect a reset of regulated plasma cortisol concentrations. Ewes were sham operated (Sham) or adrenalectomized (ADX) at ∼108 days gestation. Adrenalectomized ewes were replaced with aldosterone (3 μg ⋅ kg−1 ⋅ day−1) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1.0 mg ⋅ kg−1 ⋅ day−1); the ewes were also studied postpartum. Plasma cortisol concentrations in ADX + 0.6 ewes (5.3 ± 1.3 ng/ml) were similar to the Sham ewes postpartum (5.5 ± 0.6 ng/ml), whereas ADX + 1.0 concentrations (8.9 ± 1.0 ng/ml) were similar to pregnant Sham ewes (9.5 ± 1.9 ng/ml). Plasma ACTH concentrations were significantly increased in the pregnant ADX + 0.6 ewes (273 ± 44 pg/ml) relative to pregnant Sham ewes (84 ± 9 pg/ml) or the same ewes postpartum (42 ± 9 pg/ml). Plasma ACTH concentrations were not different among the groups postpartum. Acute increases in plasma cortisol to 15–25 ng/ml produced similar inhibition in all groups. These results suggest that pregnancy resets the basal cortisol concentration required for normalization of basal ACTH concentration.

Early Platelet-Collagen Interactions in Whole Blood and Their Modifications by Aspirin and Dipyridamole Evaluated by a New Method (Basic Wave)

1985 ◽  
Vol 54 (04) ◽  
pp. 799-803 ◽  
Author(s):  
José Luís Pérez-Requejo ◽  
Justo Aznar ◽  
M Teresa Santos ◽  
Juana Vallés
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
White Blood Cells ◽  
Reversible Aggregation ◽  
Inhibitory Compounds ◽  
Rapid Generation ◽  
Stimulation Of ◽  
Collagen Stimulation

SummaryIt is shown that the supernatant of unstirred whole blood at 37° C, stimulated by 1 μg/ml of collagen for 10 sec, produces a rapid generation of pro and antiaggregatory compounds with a final proaggregatory activity which can be detected for more than 60 min on a platelet rich plasma (PRP) by turbidometric aggregometry. A reversible aggregation wave that we have called BASIC wave (for Blood Aggregation Stimulatory and Inhibitory Compounds) is recorded. The collagen stimulation of unstirred PRP produces a similar but smaller BASIC wave. BASIC’s intensity increases if erythrocytes are added to PRP but decreases if white blood cells are added instead. Aspirin abolishes “ex vivo” the ability of whole blood and PRP to generate BASIC waves and dipyridamole “in vitro” significantly reduces BASIC’s intensity in whole blood in every tested sample, but shows little effect in PRP.

scholarly journals Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 735
Author(s):  
Laura Mihaela Trandafir ◽  
Elena Cojocaru ◽  
Mihaela Moscalu ◽  
Maria Magdalena Leon Constantin ◽  
Ingrith Miron ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Cortisol ◽  
Predictive Power ◽  
Pediatric Patients ◽  
The Body ◽  
Control Group ◽  
Homa Index ◽  
Obese Patients ◽  
Metabolic Markers ◽  
Markers Of Inflammation

Background: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. Methods: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. Results: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). Conclusions: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

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