Adrenocortical responses to corticotropin-releasing factor in the rat

1986 ◽  
Vol 64 (3) ◽  
pp. 269-272 ◽  
Author(s):  
Maurice Normand ◽  
Josée Lalonde
Keyword(s):  
Body Weight ◽  
Continuous Infusion ◽  
Time Course ◽  
Plasma Corticosterone ◽  
Corticotropin Releasing Factor ◽  
Delayed Response ◽  
Sprague Dawley ◽  
Rapid Injection ◽  
Long Time ◽  
Endogenous Release

The time course of plasma corticosterone was measured in male Sprague–Dawley rats whose endogenous release of ACTH had been blocked following rapid i.v. injections of doses ranging from 0.003 to 10 μg corticotropin-releasing factor (CRF) per rat and during i.v. infusions at rates ranging from 0.001 to 20 μg CRF∙min−1∙100 g body weight−1. The range of the dose–response curve, following rapid injection, extends from 0.01 to 0.37 μg CRF, whereas it extends over a 20 000-fold range from 0.001 to 20 ng CRF∙min−1∙100 g body weight−1 during a continuous infusion. The delayed response to a small rate of CRF could be ascribed to a relatively long time of residence of CRF in the plasma which implies that a relatively long period of time is required until a minimal plasma CRF concentration is reached after the onset of a continuous infusion of CRF at a small rate. When presented with a prolonged infusion of CRF at a large rate, the pituitary secretion of ACTH is rapidly turned on at a rate which exhibits the characteristics of a prolonged secretion at a constant large magnitude.

Distribution and metabolism of corticotropin-releasing factor in the rat

1986 ◽  
Vol 64 (6) ◽  
pp. 683-688 ◽  
Author(s):  
Bernard Candas ◽  
Josée Lalonde ◽  
Maurice Normand
Keyword(s):  
Time Course ◽  
Corticotropin Releasing Factor ◽  
Metabolic Clearance ◽  
Sprague Dawley ◽  
Rapid Injection ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
The Mean ◽  
The Moment ◽  
The One

To develop a mathematical model of the distribution and metabolism of rat corticotropin-releasing factor (rCRF), the time course of 125I-labelled rCRF in plasma was measured in male Sprague–Dawley rats (i) following a rapid injection of 24 ng rCRF/100 g body weight (BW), or (ii) following a rapid injection of 424 ng rCRF/100 g BW, or (iii) during an infusion at a rate ranging from 0.28 to0.73 ng rCRF∙min−1∙100 g BW−1. The comparison of the one-, two-, and three-compartment models shows that the two-pool structure fits better to the dynamics of CRF in plasma as measured in each rat. Following a rapid injection the decay curve occurs in a biphasic manner; the early phase of disappearance is 25 times faster than the late one. There is no significant difference between the estimates of the metabolic clearance rate following both amplitudes of injection (0.40 ± 0.06 and 0.48 ± 0.05 mL∙min−1∙100 g BW−1). The volume of the first pool, 16.8 ± 1.1 mL/100 g BW, is four times larger than the plasma volume. It would thus appear that CRF is rapidly distributed from plasma into several tissues which are represented in the first pool of the model. The mean residence time of every CRF molecule in the second compartment, from the moment of secretion to its elimination, is from three to four times longer than in the first one. It stays, on average, between 140 min and 3 h in the system before an irreversible exit. At steady state, the disposal rate represents only 3% of the CRF mass of the first compartment every minute. These results could explain the prolonged effects of CRF on pituitary-adrenocortical secretion.

Levels of 5-Bromo-2′-deoxyuridine and Its Metabolites During Continuous Infusion Paradigms in a Transplacental System

1984 ◽  
Vol 3 (1) ◽  
pp. 73-79 ◽  
Author(s):  
A. Turturro ◽  
N. P. Singh ◽  
J. Bazare ◽  
R. W. Hart
Keyword(s):  
Body Weight ◽  
Continuous Infusion ◽  
Sister Chromatid ◽  
Time Course ◽  
Sister Chromatid Exchanges ◽  
Fetal Blood ◽  
Sprague Dawley ◽  
Intraperitoneal Infusion ◽  
Chromatid Exchanges

The levels of 5-bromo-2'-deoxyuridine (BrdUrd) (a teratogen and mutagen) and its metabolites were measured using the hplc in maternal and fetal blood at 20–21 days of gestation in Sprague-Dawley derived CD rats during continuous infusion paradigms which are used in visualization of sister chromatid exchanges. The time course of the maternal values following a dose of 1 g/kg body weight was determined by sampling with an aortic catheter. Fetal levels were taken after a 2-hour intraperitoneal infusion of BrdUrd into the mother. It was found that the maternal level of BrdUrd plateaued at 0.4 mg%, while the level of metabolites gradually increased with time for both techniques. Also, although the overall amount of radioactivity indicated that approximately 40% of the total maternal dose reached the fetus, the fetal concentration of BrdUrd was less than one-seventh the maternal one.

Distribution and metabolism of adrenocorticotropin in the rat

1979 ◽  
Vol 57 (9) ◽  
pp. 1024-1027 ◽  
Author(s):  
Maurice Normand ◽  
Josee Lalonde
Keyword(s):  
Standard Error ◽  
Time Course ◽  
Compartment Model ◽  
Sprague Dawley ◽  
Mean Values ◽  
Sprague Dawley Rats ◽  
Two Compartment Model ◽  
Rapid Fall ◽  
Significant Difference ◽  
Endogenous Release

The time course of plasma bioactive adrenocorticotropin (ACTH) concentrations measured following two rapid injections of the hormone at doses of 7.5 and 22.5 mU/100 g, iv, and one infusion over a period of 80 min at a rate of 1.3 mU/min per 100 g, to male Sprague–Dawley rats whose endogenous release of ACTH had been blocked, leads to the conclusion that the hormone is distributed in two compartments. Indeed, the rapid fall of plasma ACTH concentrations in the early minutes following either the injections or the stop of the infusion is followed by a much slower phase. There is no significant difference between the measurements and the two-compartment model outputs. The model represents, on the average, the mean values of the measurements plus or minus 1 standard error for the single injections and plus or minus 1.2 standard error for the infusion.

Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist

1999 ◽  
Vol 276 (5) ◽  
pp. R1461-R1468 ◽  
Author(s):  
Gennady N. Smagin ◽  
Leigh Anne Howell ◽  
Stephen Redmann ◽  
Donna H. Ryan ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Receptor Antagonist ◽  
Acute Stress ◽  
Third Ventricle ◽  
Corticotropin Releasing Factor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sustained Reduction ◽  
Acute Responses

We previously reported that rats exposed to repeated restraint (3 h/day for 3 days) experience temporary hypophagia and a sustained reduction in body weight compared with nonrestrained controls. Studies described here determined the involvement of central corticotropin-releasing factor (CRF) receptors in the initiation of this chronic response to acute stress. In experiment 1, Sprague-Dawley rats were fitted with cannulas in the lateral ventricle and infused with 50 μg of αhCRF-(9—41) or saline immediately before restraint on each of the 3 days of restraint. The receptor antagonist inhibited hypophagia and weight loss on day 1 of restraint but not on days 2 and 3. In experiment 2, 10 μg of αhCRF-(9—41) or saline were infused into the third ventricle immediately before each restraint. The receptor antagonist totally blocked stress-induced hypophagia and weight loss. These results demonstrate that CRF receptors located in or near the hypothalamus mediate the acute responses to stress that lead to a permanent change in the hormonal or metabolic processes that determine body weight and body composition.

scholarly journals Orexigenic response to tail pinch: role of brain NPY1 and corticotropin releasing factor receptors

2014 ◽  
Vol 306 (3) ◽  
pp. R164-R174 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Yvette Taché
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Body Weight Gain ◽  
The Body ◽  
Corticotropin Releasing Factor ◽  
Sprague Dawley ◽  
Tail Pinch ◽  
Acute Response

Tail pinch stimulates food intake in rats. We investigated brain mechanisms of this response and the influence of repeated exposure. Sprague-Dawley rats received acute (5 min) or repeated (5 min/day for 14 days) tail pinch using a padded clip. Acute tail pinch increased 5-min food intake compared with control (0.92 ± 0.2 vs. 0.03 ± 0.01 g, P < 0.01). This response was inhibited by 76% by intracerebroventricular injection of BIBP-3226, a neuropeptide Y1 (NPY1) receptor antagonist, increased by 48% by astressin-B, a corticotropin-releasing factor (CRF) receptor antagonist, and not modified by S-406-028, a somatostatin subtype 2 antagonist. After the 5-min tail pinch without food, blood glucose rose by 21% ( P < 0.01) while changes in plasma acyl ghrelin (+41%) and adrenocorticotropic hormone (+37%) were not significant. Two tail pinches (45 min apart) activate pontine and hindbrain catecholaminergic and hypothalamic paraventricular CRF neurons. After 14 days of repeated tail pinch, the 5-min orexigenic response was not significantly different from days 2 to 11 but reduced by 50% thereafter ( P < 0.001). Simultaneously, the 5-min fecal pellet output increased during the last 5 days compared with the first 5 days (+58%, P < 0.05). At day 14, the body weight gain was reduced by 22%, with a 99% inhibition of fat gain and a 25% reduction in lean mass ( P < 0.05). The orexigenic response to acute 5-min tail pinch is likely to involve the activation of brain NPY1 signaling, whereas that of CRF tends to dampen the acute response and may contribute to increased defecation and decreased body weight gain induced by repeated tail pinch.

Circadian variation in response to CRF-41 and AVP

1988 ◽  
Vol 255 (3) ◽  
pp. E265-E271
Author(s):  
M. Graf ◽  
A. J. Fischman ◽  
A. J. Kastin ◽  
R. L. Moldow
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Circadian Variation ◽  
Early Morning ◽  
Plasma Corticosterone ◽  
Corticotropin Releasing Factor ◽  
Constant Darkness ◽  
Base Line ◽  
Dark Cycle ◽  
Corticosterone Response ◽  
Endogenous Release

The diurnal response to ovine corticotropin-releasing factor (CRF-41), arginine vasopressin (AVP), and adrenocorticotropic hormone (ACTH) was studied in rats in which the endogenous release of CRF was blocked by chlorpromazine, morphine sulfate, and pentobarbital sodium. This procedure resulted in a markedly attenuated circadian rhythm at base-line levels of plasma corticosterone and ACTH. Decreased pituitary responsiveness to CRF-41 and AVP at 0400 compared with 1600 was observed. The plasma corticosterone response 30 min after intravenous injection of ovine CRF-41 (0.1 microgram/kg) or AVP (5.0 micrograms/kg) remained nearly constant over the major portion of the 24-h light-dark cycle. However, in the early morning (0400), 2 h before lights on, there was an approximately threefold decrease in response. The time of this decrease in response coincided with the normal decline in the concentrations of plasma corticosterone and ACTH. Rats exposed to constant darkness for 10 days continued to show a significantly greater response to CRF or AVP at 1600 than at 0400. In contrast, rats exposed to constant light for 10 days failed to demonstrate a differential response to CRF or AVP at different times of the day. These results demonstrate that there is a diurnal rhythm in pituitary response to CRF and AVP.

scholarly journals Time-dependent mediators of HPA axis activation following live Escherichia coli

2011 ◽  
Vol 301 (6) ◽  
pp. R1648-R1657 ◽  
Author(s):  
Z. R. Zimomra ◽  
V. M. Porterfield ◽  
R. M. Camp ◽  
J. D. Johnson
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Cytokines ◽  
Hpa Axis ◽  
Time Course ◽  
Early Time ◽  
Plasma Corticosterone ◽  
Sprague Dawley ◽  
E Coli ◽  
Time Points ◽  
Early Rise

The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 × 107 CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2 was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2 correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 × 108 CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.

scholarly journals Time Course of ECG Depolarization and Repolarization Changes during Ischemia in PTCA Recordings

2004 ◽  
Vol 43 (01) ◽  
pp. 43-46 ◽  
Author(s):  
J. García ◽  
G. Wagner ◽  
R. Bailón ◽  
L. Sörnmo ◽  
P. Laguna ◽  
...  
Keyword(s):  
Time Course ◽  
Wave Amplitude ◽  
Temporal Evolution ◽  
Delayed Response ◽  
S Wave ◽  
Ecg Changes ◽  
T Complex ◽  
Karhunen Loeve Transform ◽  
Low Amplitude ◽  
Electrocardiogram Ecg

Summary Objectives: In this work we studied the temporal evolution of changes in the electrocardiogram (ECG) as a consequence of the induced ischemia during prolonged coronary angioplasty, comparing the time course of indexes reflecting depolarization and those reflecting repolarization. Methods: We considered both local (measured at specific points of the ECG) and global (obtained from the Karhunen-Loève transform) indexes. In particular, the evolution of Q, R and S wave amplitudes during ischemia was analyzed with respect to classical indexes such as ST level. As a measurement of sensitivity we used an Ischemic Changes Sensor (ICS), which reflects the capacity of an index to detect changes in the ECG. Results: The results showed that, in leads with low-amplitude ST-T complexes, the S wave amplitude was more sensitive in detecting ischemia than was the commonly used index ST60. It was found that in such leads the S wave amplitude initially exhibited a delayed response to ischemia when compared to ST60, but its performance was better from the second minute of occlusion. The global indexes describing the ST-T complex were, in terms of the ICS, superior to the S wave amplitude for ischemia detection. Conclusions: Ischemic ECG changes occur both at repolarization and depolarization, with alterations in the depolarization period appearing later in time. Local indexes are less sensitive to ischemia than global ones.

scholarly journals The long-term course of fatigue following breast cancer diagnosis

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Karin Biering ◽  
Morten Frydenberg ◽  
Helle Pappot ◽  
Niels Henrik Hjollund
Keyword(s):  
Breast Cancer ◽  
Time Course ◽  
Breast Cancer Diagnosis ◽  
Patient Characteristics ◽  
Repeated Measurements ◽  
Diagnosis And Treatment ◽  
Persistent Problem ◽  
Treatment Regimens ◽  
Long Time

Abstract Purpose Fatigue following breast cancer is a well-known problem, with both high and persistent prevalence. Previous studies suffer from lack of repeated measurements, late recruitment and short periods of follow-up. The course of fatigue from diagnosis and treatment to the long-time outcome status is unknown as well as differences in the level of fatigue between treatment regimens. The purpose of this study was to describe the long-time course of fatigue from the time of clinical suspicion of breast cancer, its dependence of patient characteristics and treatment regimens and the comparison with the course of fatigue among women with the same suspicion, but not diagnosed with breast cancer. Methods Three hundred thirty-two women referred to acute or subacute mammography was followed with questionnaires from before the mammography and up to 1500 days. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI-20). The women reported their initial level of fatigue before the mammography and thus without knowledge of whether they had cancer or not. Both women with and without cancer were followed. Women with cancer were identified in the clinical database established by Danish Breast Cancer Cooperative Group (DBCG) to collect information on treatment regimen. Results Compared to fatigue scores before diagnosis, women with breast cancer reported a large increase of fatigue, especially in the first 6 months, followed by a slow decrease over time. Despite the long follow-up period, the women with breast cancer did not return to their level of fatigue at time of the mammography. Women without breast cancer, experienced a rapid decrease of fatigue after disproval of diagnosis followed by a steadier period. Conclusions Fatigue is a persistent problem in women diagnosed with breast cancer, even several years following diagnosis and treatment. The women with breast cancer were most affected by fatigue in the first 6 months after diagnosis.

Sign in / Sign up

Export Citation Format

Share Document