Pituitary-adrenal function in the immature ovine foetus

1995 ◽  
Vol 145 (3) ◽  
pp. 455-460 ◽  
Author(s):  
A C McFarlane ◽  
S Potocnik ◽  
M Towstoless ◽  
K Moritz ◽  
E M Wintour
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Intravenous Infusion ◽  
Adrenal Function ◽  
Short Term ◽  
Releasing Hormone ◽  
Basal Cortisol ◽  
Cortisol Levels

Abstract Pituitary-adrenal responses to intravenous infusion of ovine corticotrophin-releasing hormone (oCRH) or arginine vasopressin (AVP) and to haemorrhage were examined in the ovine foetus prior to 90 days of gestation (term 145–150 days). In chronically cannulated foetuses (n=8), between 74 and 84 days of gestation, basal ACTH levels were less than 20 pg/ml while cortisol levels were 6·5 ± 1·5 nmol/l (mean±s.e m.). Intravenous infusion of oCRH (1 μg/h for 60 min) or AVP (1 μg/h for 60 min) significantly increased ACTH (P<0·05 for both treatments) and cortisol (P<0·01 for both treatments) levels, although the response to both hormones was modest. In acutely studied foetuses of a similar age (70–90 days of gestation, mean 82·0 ± 1·4 days, n=7), exteriorization and progressive haemorrhage significantly (P<0·05) elevated ACTH levels from 117·4 ± 32·1 pg/ml to a maximal value of 329·2 ± 112·8 pg/ml, the maximal ACTH response corresponding to the removal of a volume of blood equivalent to 6·6 ±1·2% of the pre-haemorrhage body weight. The present study has demonstrated that the ovine foetal pituitary, in vivo, is responsive to exogenous and endogenous stimuli by mid-gestation and, at this age, although basal cortisol levels are low, the foetal adrenal is capable of responding to elevated ACTH levels in the short term. Journal of Endocrinology (1995) 145, 455–460

scholarly journals Desensitization of the adrenocorticotrophin responses to arginine vasopressin and corticotrophin-releasing hormone in ovine anterior pituitary cells

2003 ◽  
Vol 178 (3) ◽  
pp. 491-501 ◽  
Author(s):  
A Hassan ◽  
S Chacko ◽  
D Mason
Keyword(s):  
Arginine Vasopressin ◽  
Anterior Pituitary ◽  
Prolonged Exposure ◽  
No Reduction ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells

Following repeated or prolonged exposure to either corticotrophin-releasing hormone (CRH) or arginine vasopressin (AVP), pituitary adrenocorticotrophin (ACTH) responsiveness is reduced. This study compared the characteristics of desensitization to CRH and AVP in perifused ovine anterior pituitary cells. Desensitization to AVP occurred at relatively low AVP concentrations and was both rapid and readily reversible. Treatment for 25 min with AVP at concentrations greater than 2 nM caused significant reductions in the response to a subsequent 5 min 100 nM AVP pulse (IC(50)=6.54 nM). Significant desensitization was observed following pretreatment with 5 nM AVP for as briefly as 5 min. Desensitization was greater following a 10 min pretreatment, but longer exposures caused no further increase. Resensitization was complete within 40 min following 15 min treatment with 10 nM AVP. Continuous perifusion with 0.01 nM CRH had no effect on AVP-induced desensitization. Treatment with 0.1 nM CRH for either 25 or 50 min caused no reduction in the response to a subsequent 5 min stimulation with 10 nM CRH. When the pretreatment concentration was increased to 1 nM significant desensitization was observed, with a greater reduction in response occurring after 50 min treatment. Recovery of responsiveness was progressive following 50 min treatment with 1 nM CRH and was complete after 100 min. Our data show that in the sheep AVP desensitization can occur at concentrations and durations of AVP exposure within the endogenous ranges. This suggests that desensitization may play a key role in regulating ACTH secretion in vivo. If, as has been suggested, CRH acts to set corticotroph gain while AVP is the main dynamic regulator, any change in responsiveness to CRH may significantly influence the overall control of ACTH secretion.

Consistent Reduction of ACTH responses to stimulation with CRH, Vasopressin and Hypoglycaemia in Patients with Major Depression

1989 ◽  
Vol 155 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Roger G. Kathol ◽  
Richard S. Jaeckle ◽  
Juan F. Lopez ◽  
William H. Meller
Keyword(s):  
Major Depression ◽  
Hpa Axis ◽  
Negative Correlation ◽  
Arginine Vasopressin ◽  
Corticotropin Releasing Hormone ◽  
Hypothalamic Pituitary Adrenal ◽  
Releasing Hormone ◽  
Control Subjects ◽  
Basal Cortisol ◽  
Cortisol Responses

Eleven patients with major depression and 12 control subjects were administered corticotropin-releasing hormone (CRH), aqueous arginine vasopressin (AVP), and insulin hypoglycaemia (IH) to test for differences in hypothalamic–pituitary–adrenal (HPA) axis function. Patients with major depression demonstrated lower ACTH responses to CRH when compared with controls, and a trend toward such after administration of AVP. Despite lower ACTH responses in patients with depression, there were no differences in Cortisol responses to these stimuli. In the CRH and AVP tests, there was no correlation between the basal Cortisol and ACTH responses in either controls or patients, but in the IH test there was a negative correlation between these responses for both groups. The ACTH responses to CRH and AVP were positively correlated in controls and patients. Cortisol responses to all three provocative stimuli were positively correlated in both subject groups. These findings are consistent with the hypothesis that hypothalamic or supra-hypothalamic overactivity may be involved in the development of HPA-axis abnormalities in patients with depression.

Direct effect of physiological doses of arginine vasopressin on the arterial wall in vivo

1978 ◽  
Vol 234 (2) ◽  
pp. H167-H172 ◽  
Author(s):  
E. Monos ◽  
R. H. Cox ◽  
L. H. Peterson
Keyword(s):  
Arginine Vasopressin ◽  
Flow Resistance ◽  
Arterial Wall ◽  
External Diameter ◽  
Short Term ◽  
Before And After ◽  
Circulatory Control ◽  
Anesthetized Dogs ◽  
Vascular Beds

Effects of topically applied arginine vasopressin (VPA), in 100-150 muU/ml blood concentration, on external diameter (D) and on dynamic elastic modulus (E*) of surgically denervated common carotid (CC) and femoral (FA) arteries have been studied before and after hypophysectomy in anesthetized dogs. Changes in D, E*, and flow resistance (R) of the CC and FA vascular beds before and after removal of the pituitary were also determined. It was found that VPA elicited a substantial (max 21-26%) decrease in E* and a smaller (max 5.9-6.9%) reduction in D of FA independent of the presence of absence of the pituitary gland. The VPA effect developed more rapidly after hypophysectomy than before. In the CC, VPA did not significantly affect values of E*. During the 1-h period after hypophysectomy, statistically significant decreases in E*-CC, E*-FA, and D-CC were observed, but D-FA did not change, although arterial pressure as well as R-FA and R-CC were diminished. These results give further support to physiological vascular actions of VPA and a possible role in short-term circulatory control. In large arteries, the effects of VPA also seem to be regionally differentiated.

Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function

1995 ◽  
Vol 144 (2) ◽  
pp. 301-310 ◽  
Author(s):  
U Knutsson ◽  
P Stierna ◽  
C Marcus ◽  
J Carlstedt-Duke ◽  
K Carlström ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Adrenal Function ◽  
Systemic Effects ◽  
Mrna Levels ◽  
Urinary Cortisol ◽  
Short Term ◽  
Central Function ◽  
Peripheral Lymphocytes ◽  
Long Term Treatment ◽  
Cortisol Levels

Abstract Glucocorticoids are among the most potent anti-inflammatory agents that can be used in the treatment of rhinitis. Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids. In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks. Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay. Serum cortisol, osteocalcin and urinary cortisol levels were also determined. An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response. In peripheral lymphocytes, GR mRNA levels were significantly down-regulated. MTIIa mRNA levels increased significantly. Serum osteocalcin decreased significantly during treatment with both BUD and FP. Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment. In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes. These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact. Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids. Journal of Endocrinology (1995) 144, 301–310

Physiological dosing of exogenous ACTH

1985 ◽  
Vol 108 (3) ◽  
pp. 401-406 ◽  
Author(s):  
Michael L. Graybeal ◽  
Victor S. Fang
Keyword(s):  
Body Weight ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Cortisol Responses ◽  
Cortisol Levels ◽  
Physiologic Responses

Abstract. We evaluated the ACTH and cortisol responses to several doses of exogenous ACTH, and compared these values to the physiologic responses obtained in normal subjects undergoing insulin-induced hypoglycaemia. We determined that a cosyntrophin dose of 0.2 μg/kg body weight produced both ACTH and cortisol levels indistinguishable from the 'physiologic' stress-induced values. Since this dose is approximately 4 per cent of the standard 250 μg dose employed in tests of adrenal function, our findings suggest a need for caution in the interpretation of such tests.

Reduced osmotic and nonosmotic release of vasopressin after meclofenamate in the conscious dog

1986 ◽  
Vol 250 (6) ◽  
pp. R1028-R1033
Author(s):  
B. R. Walker ◽  
A. L. Erickson ◽  
P. E. Arnold ◽  
T. J. Burke ◽  
T. Berl
Keyword(s):  
Hypertonic Saline ◽  
Arginine Vasopressin ◽  
Intravenous Infusion ◽  
In Vitro Experiments ◽  
Synthesis Inhibition ◽  
Conscious Dog ◽  
Osmotic Stimulus ◽  
Saline Vehicle

Both in vivo as well as in vitro experiments suggest that prostaglandins (PG) may influence arginine vasopressin (AVP) release. Recent studies on conscious dogs have shown that cyclooxygenase inhibition with meclofenamate reduces basal AVP release as well as AVP release in response to hypoxia. The current experiments were performed in order to test whether PG synthesis inhibition affects osmotic- and nonosmotic-stimulated AVP release in a similar manner. Osmotic AVP release was tested by slowly infusing hypertonic saline intravenously in water-diuresing dogs and serially sampling plasma for AVP concentration. Experiments were performed both with and without meclofenamate (2 mg/kg and 2 mg X kg-1 X h-1 iv) pretreatment. AVP release to a comparable osmotic stimulus was greatly reduced after meclofenamate administration. Nonosmotic AVP release was tested by inducing systemic hypotension with an intravenous infusion of nitroprusside. Hypotension was associated with an increase in AVP concentration, which was partially blunted after meclofenamate administration. Experiments performed with only a saline vehicle administered showed no decrease in AVP release in response to comparable hypotension. The findings of these studies suggest that endogenous PG may be involved in both osmotic and nonosmotic AVP release in the conscious dog.

Apoptosis signal ceramide c6 synergizes anti-tumor effects of paclitaxel oxaliplatin & cisplatin on growth of pancreatic cancer in SCID mice

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13135-13135
Author(s):  
D. Shrayer ◽  
H. J. Wanebo ◽  
M. Resnick
Keyword(s):  
Body Weight ◽  
Caspase 3 ◽  
Combined Therapy ◽  
Drug Dose ◽  
Scid Mice ◽  
Short Term ◽  
Short Term Exposure ◽  
Chemical Studies

13135 Background: Ceramide (C6) is an analog of endogenous ceramides, which are a major signaling pathway for apoptosis in cells undergoing stress, exposure to chemotherapy. Current report documents in vivo anti tumor effects combining C6 with oxaliplatin & cisplatin on L3.6 human pancreatic adenocarcinoma implanted in the SCID mouse. Correlative histologic studies provide additional mechanistic insights. Methods: SCID/Beige/ Taconicmale mice were inoculated subcutaneously (S.C.) w/2×106 L3.6 pancreatic cells. Chemotherapy doses were based on clinical & in vitro data. Treatment began 4 days post tumor implant with 3 weekly 3×/wk) intraperitoneal (IP) injections of Paclitaxel (P) 3.0 m/kg, oxaliplatin (OX) 2.5 mg/kg, cisplatin (CP) 2.5 mg/kg, with/without ceramide 10 mg/kg. Mice were observed for 6 weeks & were autopsied when near death, or at 6 week level. (All controls died by 3rd week). Data recovered included maximum tumor volume, tumor weight, body weight & survival. Histopathology studies were carried out in a separate group of 40 mice treated by the same drug dose levels & autopsied at 4 hours & 24 hours. Tumors were bi-valved & fixed in buffered formalin or frozen in hexane/acetone bath. Major focus was effects on tumor necrosis, apoptosis, mitotic index & Apoptosis (caspase 3 expression) index. Results: Combination w/C6 ceramide augmented the tumor reduction obtained by chemotherapy alone by 57% (while preserving body weight), & increased 6 wk survival from 0% (Chemotherapy alone) to 60% w/combined therapy. Mean survival was increased from 25 to 37 days. Preliminary short term immunohisto chemical studies showed enhancement of apoptotic index by increased and caspase 3 expression at 4 & 24 hr by ceramide combinations. Conclusion: Combination therapy w/C6 Ceramide significantly enhanced anti tumor response to Paclitaxel, Oxaliplatin & Cisplatin in SCID Mice bearing L3.6 pancreatic tumor implants. Early development of enhanced apoptosis by caspase 3 expressions was shown in preliminary short term exposure experiments. No significant financial relationships to disclose.

Plasma concentrations of adrenocorticotropin-related peptides after corticotropin-releasing hormone and vasopressin injections in sheep

1988 ◽  
Vol 119 (3) ◽  
pp. 391-396 ◽  
Author(s):  
P. Pradier ◽  
M. Dalle ◽  
C. Tournaire ◽  
P. Delost
Keyword(s):  
Body Weight ◽  
Column Chromatography ◽  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Molecular Forms ◽  
Pituitary Cells ◽  
Plasma Samples ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Simultaneous Injection

Abstract. Ovine corticotropin-releasing hormone (1 μg/kg body weight) and arginine vasopressin (1 μg/kg) were injected iv in sheep, both separately and in combination. Plasma were sampled just before and 5, 15 and 30 min after the injection. Adrenocorticotropin-related peptides were isolated by Sephadex G-50 column chromatography and measured by RIA. Cortisol and aldosterone were determined on the same plasma samples. Three molecular forms of immunoreactive ACTH (IR-ACTH) were isolated: 'big' (> 20 000 mol wt), 'intermediate' (= 8000 mol wt) and 'little' (= 4500 mol wt). Following CRH injections, the three molecular forms of ACTH were enhanced, particularly the 'little' form, whereas 'intermediate' IR-ACTH was highly and specifically responsive to AVP. After a simultaneous injection of CRH and AVP, additive increases occurred for 'intermediate' and 'little' IR-ACTH. The release of different molecular forms of IR-ACTH after stimulation by CRH or AVP of corticotrope cells suggests that ACTH-related peptides could be stored in different intracellular pools or secreted by different pituitary cells.

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