TSH and ACTH Secretion and Cyclic Adenosine 3'5' Monophosphate Content following Stimulation with TRH or Lysine Vasopressin in Vitro: Suppression by Thyroxine and Dexamethasone

1978 ◽  
Vol 158 (4) ◽  
pp. 524-529 ◽  
Author(s):  
J. C. Rose ◽  
P. M. Conklin
Keyword(s):  
Acth Secretion ◽  
Lysine Vasopressin

Early glucocorticoid feedback in anterior pituitary corticotrophs: differential inhibition of hormone release induced by vasopressin and corticotrophin-releasing factor in vitro

1991 ◽  
Vol 129 (2) ◽  
pp. 261-268 ◽  
Author(s):  
M. J. Shipston ◽  
F. A. Antoni
Keyword(s):  
Anterior Pituitary ◽  
Actinomycin D ◽  
Feedback Inhibition ◽  
Female Rats ◽  
Hormone Release ◽  
Type Ii ◽  
Acth Secretion ◽  
Corticotrophin Releasing Factor ◽  
Acth Release

ABSTRACT Vasopressin and 41-residue corticotrophin-releasing factor (CRF-41) are physiological mediators of the hypothalamic control of pituitary ACTH secretion, whilst adrenocortical glucocorticoids are the major inhibitory factors regulating ACTH output. In the present study it was investigated in vitro whether the characteristics of early glucocorticoid inhibition of stimulated ACTH secretion would differ depending on the nature of the stimulus and the temporal relationship between secretagogue and steroid. The experiments were carried out using perifused segments of rat adenohypophysis obtained from randomly cycling female rats. Repeated pulses (5 min) of CRF-41 or vasopressin were given at 1-h intervals for up to 7 h. The net release of ACTH became stable after the second secretagogue pulse. Administration of 0·1 μmol corticosterone/l 30 min before and during a 5-min pulse of 10 nmol CRF-41/l inhibited CRF-41-stimulated ACTH release to 60% of control. Stimulated hormone release remained suppressed at 90 min after the start of the corticosterone infusion and returned to control levels by 150 min. If corticosterone treatment (35 min total exposure) was started simultaneously with the CRF-41 pulse, no inhibitory effect of the steroid was observed at any subsequent time-point examined (60,90,120 and 150 min). In contrast, vasopressin-stimulated ACTH release was inhibited by approximately 50% when corticosterone was applied before, or simultaneously with, a 5-min pulse of 10 nmol vasopressin/l. The synthetic glucocorticoid type II receptor agonist RU28362, administered 30 min before and during a 5-min pulse of 10 nmol CRF-41/l, reduced CRF-41-stimulated ACTH release to 50% of control up to 2·5 h after the start of RU28362 application (although inhibition after 35 min exposure was not statistically significant). Inhibition of ACTH release stimulated by 10 nmol vasopressin/l was observed within 35 min of steroid application and was maintained up to 2·5 h after the initial application of RU28362. The action of RU28362 on CRF-41-stimulated ACTH release was blocked by inhibitors of transcription (actinomycin D) and translation (puromycin); notably these drugs did not modify the ACTH response to CRF-41. In contrast, actinomycin D as well as puromycin reduced vasopressin-stimulated ACTH release. The data suggest that: (1) the timing of steroid application is important in determining the early glucocorticoid inhibition of CRF-41- but not vasopressin-stimulated ACTH secretion; (2) CRF-41 and vasopressin mobilize different pools of ACTH from the anterior pituitary gland; (3) type II glucocorticoid receptors and synthesis of new protein(s) are involved in the early inhibitory action of glucocorticoids; (4) depending on the timing and nature of the incident secretagogue, differential negative feedback inhibition of ACTH secretion may occur at the pituitary level in vivo. Journal of Endocrinology (1991) 129, 261–268

THE UPTAKE OF TRITIATED LYSINE VASOPRESSIN BY RAT AND PIG PITUITARY NEURAL LOBES IN VITRO

1971 ◽  
Vol 50 (4) ◽  
pp. 669-677 ◽  
Author(s):  
B. A. EDWARDS
Keyword(s):  
Tap Water ◽  
Exchange Chromatography ◽  
Control Group ◽  
Breakdown Product ◽  
Nacl Solution ◽  
Water Control ◽  
Neural Lobe ◽  
Lysine Vasopressin ◽  
And Control

SUMMARY Uptake of tritiated lysine vasopressin ([3H]LVP) was studied in halved neural lobes of rats (which had been given either tap water (control group) or 2% (w/v) NaCl solution as drinking water for 4 days) as well as in slices of pig neural lobe. Uptake of radioactivity into the neural lobes was shown but analysis of the extracts of incubated lobes of both species by ion exchange chromatography showed that very little of it remained in the tissue as hormone. In addition, some radioactivity was associated with trichloroacetic acid-insoluble proteins. After 90 min of incubation, and after correction for the breakdown, the uptake of unchanged [3H]LVP, expressed as a tissue: medium ratio, was 0·14 ± 0·04 and 0·09 ± 0·03 (mean ± s.e.m.) for the saline-treated and control rats respectively, while the tissue: medium ratios for the breakdown product(s) were 6·47 ± 0·45 and 5·50 ± 0·36. The results suggest uptake of [3H]LVP into the cell with almost complete intracellular breakdown of the hormone.

Regulation of CRH-induced secretion of ACTH and corticosterone by SOM230 in rats

2005 ◽  
Vol 153 (3) ◽  
pp. R7-R10 ◽  
Author(s):  
A P Silva ◽  
P Schoeffter ◽  
G Weckbecker ◽  
C Bruns ◽  
H A Schmid
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Corticotropin Releasing Hormone ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Corticosterone Secretion ◽  
Corticosterone Release ◽  
Acth Release

Objective: Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is biochemically characterized by increased plasma concentrations of ACTH inducing hypersecretion of cortisol. Somatostatin is known to inhibit ACTH secretion, and in vitro data have shown the inhibition of ACTH secretion by agonists activating sst2 and sst5 receptors. The present study aimed to determine the inhibitory effect of the multireceptor ligand SOM230, compared with the sst2-preferring agonist octreotide, on corticotropin-releasing hormone (CRH)-stimulated secretion of ACTH and corticosterone in rats. Methods: Secretion of ACTH and corticosterone was induced by i.v. application of CRH (0.5 μg/kg) in rats pretreated 1 h before by i.v. application of SOM230 (1, 3, or 10 μg/kg), octreotide (10 μg/kg) or NaCl 0.9%. Results: SOM230 (3 and 10 μg/kg) inhibited CRH-induced ACTH release by 45±3% and 51±2%, respectively, and corticosterone release by 43±5% and 27±16%, respectively. 10 μg/kg of octreotide tended to be less potent at inhibiting ACTH release (34±6% inhibition) and did not alter the secretion of corticosterone. Conclusion: SOM230 has a stronger inhibitory effect on ACTH and corticosterone secretion than octreotide in rats. This difference can be explained by its higher affinity to sst1, sst3 and especially sst5 receptors compared with octreotide.

In vitro effects of ketoconazole on corticotrope cell morphology and ACTH secretion of two pituitary adenomas removed from patients with Nelson's syndrome

1989 ◽  
Vol 121 (2) ◽  
pp. 185-190 ◽  
Author(s):  
L.Jimenez Reina ◽  
A. Leal-Cerro ◽  
J. Garcia ◽  
P.P. Garcia-Luna ◽  
R. Astorga ◽  
...  
Keyword(s):  
Volume Density ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Nelson’S Syndrome ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Nelson's Syndrome ◽  
In Vitro Effects ◽  
Intracellular Changes

Abstract. The direct effects of ketoconazole on the secretion of ACTH by human pituitary adenoma cells from 2 patients with Nelson's syndrome were studied in vitro. Stereologically quantified, intracellular changes affect the surface density of the endoplasmic reticulum (it decreased by 73%), the volume density of the secretion granules (it decreased by 49%), and the volume density of lysosomes (it decreased by 67%). The hormone released in the culture medium decreased depending on the doses of ketoconazole used; 10 μmol/l decreased ACTH levels by 31%. These data show that ketoconazole induce marked changes on corticotrope morphology and ACTH secretion in pituitary cells obtained from patients with Nelson's syndrome.

Octreotide exerts different effects in vivo and in vitro in Cushing's disease

1994 ◽  
Vol 130 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Günter K Stalla ◽  
Steffi J Brockmeier ◽  
Ulrich Renner ◽  
Chris Newton ◽  
Michael Buchfelder ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Dependent Manner ◽  
Acth Secretion ◽  
Adenoma Cell ◽  
Cortisol Levels ◽  
Corticotropic Adenoma

Stalla GK, Brockmeier SJ, Renner U, Newton C, Buchfelder M, Stalla J, Müller OA. Octreotide exerts different effects in vivo and in vitro in Cushing's disease. Eur J Endocrinol 1994;130:125–31. ISSN 0804–4643 The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on adrenocorticotropin (ACTH) secretion was studied in five patients with untreated Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in vitro. For the in vivo study, 100 μg of octreotide sc was given 30 and 180 min after cannulation of the cubital vein and 100 μg of corticotropin-releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol levels were measured for 390 min. In vivo, octreotide had no significant effect either on basal or CRH-stimulated ACTH levels and did not influence cortisol levels. The in vitro studies were conducted with corticotropic adenoma cell cultures derived from adenoma tissue obtained from six patients with Cushing's disease. In four of six cell cultures, octreotide (1 nmol/l–1 μmol/l) inhibited basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to 92% for 1 nmol/l octreotide to 14–46% for 1 μmol/l octreotide as compared to controls (100%). In three of three octreotide-responsive adenoma cell cultures investigated, CRH-stimulated ACTH secretion was suppressed by octreotide. Hydrocortisone pretreatment in vitro abolished the inhibitory effect of octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma cell culture. In conclusion, we showed that octreotide in most cases could inhibit the ACTH release from human corticotropic adenoma cells in vitro but had no suppressive effect on ACTH levels of patients with Cushing's disease in vivo. This discrepancy could be due to a somatostatin receptor down-regulation by cortisol at the hypercortisolemic state in vivo. Günter K Stalla, Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 10, D-80804 Munich, Germany

Effect of brain monoamines on the secretion of adrenocorticotrophic hormone

1982 ◽  
Vol 101 (2) ◽  
pp. 180-186 ◽  
Author(s):  
Alka Amar ◽  
S. Mandal ◽  
A. K. Sanyal
Keyword(s):  
Dopaminergic Neurons ◽  
Adrenal Glands ◽  
Plasma Corticosterone ◽  
Albino Rats ◽  
Adrenocorticotrophic Hormone ◽  
Brain Monoamines ◽  
Acth Secretion ◽  
Acute Increase

Abstract. The role of brain monoamines (5-HT, NA and DA) in the secretion of adrenocorticotrophic hormone (ACTH) was studied in view of contradictory reports. Plasma corticosterone levels and the rate of synthesis of corticosterone in vitro by the adrenal gland were estimated in albino rats and have been taken as the index of ACTH activity. These estimations were done in unstressed and stressed, and in untreated and treated rats. Drugs were administered intracerebroventricularly to the rats to cause selective degeneration of tryptaminergic, noradrenergic or dopaminergic neurons. The results show that plasma corticosterone levels and the rate of synthesis of corticosterone were significantly decreased after selective degeneration of tryptaminergic neurons in unstressed rats. After selective degeneration of either tryptaminergic or noradrenergic neurons, the acute increase in the plasma corticosterone levels and rate of synthesis of corticosterone in vitro by adrenal glands in stressed rats were significantly inhibited. These results have been interpreted to suggest that the central tonic control on adrenal glands may be 5-HT mediated and that during stress ACTH secretion may be both 5-HT and NA mediated. DA does not seem to have significant role in the regulation of ACTH secretion.

80. Potent antiglucocorticoid activity of RU38486 on acth secretion in vitro and in vivo in the rat

1982 ◽  
Vol 17 (3) ◽  
pp. xxvii ◽  
Author(s):  
L. Proulx-Ferland ◽  
J. Côté ◽  
D. Philibert ◽  
R. Deraedt
Keyword(s):  
Acth Secretion

Levoketoconazole, the 2S,4R Enantiomer of Ketoconazole, a New Steroidogenesis Inhibitor for Cushing’s Syndrome Treatment

2021 ◽  
Author(s):  
Sara G Creemers ◽  
Richard A Feelders ◽  
Frank H de Jong ◽  
Gaston J H Franssen ◽  
Yolanda B de Rijke ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Syndrome ◽  
Cell Number ◽  
Cushing's Syndrome ◽  
Variable Degree ◽  
Acth Secretion ◽  
Adrenal Steroid ◽  
Liquid Chromatography Tandem Mass ◽  
Ic50 Values

Abstract Introduction Racemic ketoconazole (RK) is a steroidogenesis inhibitor used for treatment of Cushing’s syndrome. Levoketoconazole (COR-003), the pure 2S,4R enantiomer, is potentially more potent and safe compared to RK. We compared in vitro effects of levoketoconazole and RK on adrenocortical and pituitary adenoma cells. Materials and methods HAC15 cells and 15 primary human neoplastic adrenocortical cultures (+/- ACTH), and murine (AtT20) and human corticotroph adenoma cultures were incubated with levoketoconazole or RK (0.01-10µM). Cortisol and ACTH were measured using a chemiluminescence immunoassay system, and steroid profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results In HAC15, levoketoconazole inhibited cortisol at lower concentrations (IC50: 0.300µM) compared to RK (0.611µM; P<0.0001). IC50 values of levoketoconazole for basal cortisol production in primary adrenocortical cultures varied over a 24-fold range (0.00578µM to 0.140µM), with in two patients a higher sensitivity of levoketoconazole versus RK (2.1- and 3.7-fold). LC-MS/MS analysis in selected cases revealed more potent inhibition of cortisol and other steroid profile components by levoketoconazole versus RK. In AtT20, levoketoconazole inhibited cell growth and ACTH secretion (10µM: -54% and -38%, respectively), and levoketoconazole inhibited cell number in one of two primary human corticotroph pituitary adenoma cultures (-44%, P<0.001). Conclusion Levoketoconazole potently inhibits cortisol production in adrenocortical cells, with a variable degree of suppression between specimens. Levoketoconazole inhibits adrenal steroid production more potently compared to RK and might also inhibit ACTH secretion and growth of pituitary adenoma cells. Together with previously reported potential advantages, this indicates that levoketoconazole is a promising novel pharmacotherapy for Cushing’s syndrome.

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