Effects of angiotensin II and ACTH on normal and tumourous human adrenocortical cells

Belmega, Wolfgang; Oelkers, W.; Belkien, L.; Shirpai, Monika; Fiedler, U.; Häring, Rudolf

doi:10.1530/acta.0.1040103

Cited by 10 publications

(6 citation statements)

References 15 publications

(20 reference statements)

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“…(12). However, the cell preparations used in the present study were less sensitive to corticotropin.…”

Section: Discussioncontrasting

confidence: 50%

“…2). The detailed procedure of cell preparation and incubation in this laboratory has been described in detail by Belmega et al (12). About 2 l O 5 cells (about 90% viable according to trypan-blue exclusion) were incubated in 2 ml medium for 2 hours in a metabolic shaker (Warburg Apparat, type 585G, Braun Melsungen, FRG) under a stream of 95% O 2 and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of β-Lipotropin, β-Endorphin, γ2-Melanotropin and Corticotropin on Steroid Production by Isolated Human Adrenocortical Cells

Eggens

Bähr²,

Oelkers³

et al. 1987

Clinical Chemistry and Laboratory Medicine

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Summary:Normal human adrenocortical cells (from multi-organ donors) were incubated with corticotropin (tetracosactide), highly purified human ß-lipotropin, synthetic human ß-lipotropin, y 2 -melanocyte stimulating hormone and ß-endorphin. Corticotropin stimulated cortisol, aldosterone and 18-hydroxycorticosterone production starting at " 12 -10" 11 mol/1 in normal adrenocortical cells. Purified human ß-lipotropin also stimulated steroidogenesis but 100 -lOOOfold higher concentrations of the peptide were needed. In contrast, synthetic human ß-lipotropin was without any effect on steroid production up to concentrations of 10~? mol/1. Synthetie ß-lipotropin (5 10~1 0 mol/1) did not significantly change the dose-response curve for corticotropin (10~1 3 mol/1-10~9 mol/1) versus the three steroids ineasured. y 2 -Melanotropin and ß-endorphin (10~6 mol/1) stimulated the secretion of cortisol, but not of aldosterone.Since synthetic human ß-lipotropin has no effect on human adrenocortical cells, the purified ß-lipotropin must be contaminated with traces of eorticotropin. Since pathologically elevated levels of proopipmelanocortin-derived peptides will rarely exceed plasma concentrations of 10~1 0 mol/1, our findings in vitro do not support a physiological or pathophysiological role of the peptides examined in the regulation of adrenal steroid secretion.

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“…(12). However, the cell preparations used in the present study were less sensitive to corticotropin.…”

Section: Discussioncontrasting

confidence: 50%

Section: Methodsmentioning

confidence: 99%

Effects of β-Lipotropin, β-Endorphin, γ2-Melanotropin and Corticotropin on Steroid Production by Isolated Human Adrenocortical Cells

Eggens

Bähr²,

Oelkers³

et al. 1987

Clinical Chemistry and Laboratory Medicine

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“…There was no difference in sensitivity to A11 between tumour and cortex. In vitro stimulation of cortisol production by human adrenocortical cells by A11 has been reported previously (Brown et al 1980;Belmega et al 1983). In bovine adrenocortical cells, the secretion of cortisol in response to A11 is associated with the activation of phosphoinositidase-C and an increase in free intracellular Ca2+, resulting in enhanced expression of P-45017a, and is apparently mediated via type 1 A11 receptors on zona fasciculata cells (Bird et al 1992).…”

Section: Discussionmentioning

confidence: 77%

CORTISOL PRODUCTION BY ALDOSTERONE‐PRODUCING ADENOMAS IN VITRO

Stowasser

Tunny

Klemm

et al. 1993

Clin Exp Pharma Physio

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1. In vitro short-term production of cortisol by dispersed tumour and non-tumourous adrenal cortical cells was measured with and without added angiotensin II (AII) or adrenocorticotrophin (ACTH) in adrenals removed from five patients with primary aldosteronism. 2. Aldosterone-producing adenomas (APA) were classified as angiotensin responsive (AII-R) or angiotensin unresponsive (AII-U) based on pre-operative behaviour in vivo. 3. Cortisol was produced by both tumour and cortex in vitro without stimulation, and significantly more cortisol was generated by the cortex. 4. Addition of AII significantly increased cortisol production by both tumour and cortex to an equal extent. 5. Addition of ACTH also significantly increased cortisol production by both tumour and cortex, but tumours were more responsive than cortex. The response to ACTH exceeded the response to angiotensin in both tumour and cortex. 6. There was no obvious difference between AII-R and AII-U APA in terms of cortisol production.

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“…The injection of 10 pg ACTH resulted in a rise of plasma ACTH to 12.2 pmol/1 and in an increase in plasma cortisol by 157% and in plasma aldosterone by 114%. In vitro human adrenocortical cells were stimulated by 10 pmol/1 ACTH to a 350% increase in cortisol secretion and a 100% increase in aldoste¬ rone secretion (15). The sensitivity of the stimula¬ tion by AVP of cortisol secretion from guinea pig adrenal cells (16) and of aldosterone secretion from rat adrenal glomerulosa cells (17) is higher.…”

Section: Discussionmentioning

confidence: 99%

“…After having given informed consent according to the Declaration of Helsinki, 15 normal men (between 21 and 32 years of age, body weights between 65 and 84 kg) participated in the study. All were non-smokers and on an unrestricted diet.…”

Section: Methodsmentioning

confidence: 99%

Stimulation of steroid secretion by adrenocorticotropin injections and by arginine vasopressin infusions: no evidence for a direct stimulation of the human adrenal by arginine vasopressin

Bähr

Hensen²,

Hader³

et al. 1991

Acta Endocrinologica

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Arginine vasopressin stimulates the secretion of adrenocorticotropin. A direct stimulatory effect of AVP on cortisol as well as aldosteron secretion has been postulated by several investigators. To study the possible role of a direct stimulatory action of AVP on the adrenal cortex, normal volunteers were treated with incremental injections of ACTH or with incremental infusions of AVP which raised plasma AVP levels to a maximum of 256\m=+-\16 pmol/l. In both situations, a significant (p<0.001) linear correlation between plasma ACTH and plasma cortisol was observed. The regression coefficients were not different (p>0.5). Plasma aldosterone was stimulated by both treatments, but the weakly positive correlation between plasma ACTH and plasma aldosterone was not significant for either stimulus. Thus, in man, a direct stimulatory effect of AVP on cortisol secretion cannot be demonstrated. A direct effect of AVP on aldosterone cannot be definitely excluded, but is certainly of minor importance.Arginine vasopressin is known to stimulate adre¬ nocorticotropin in man (1,2). Besides elevating plasma ACTH, AVP also induces a rise in plasma cortisol. The question whether this steroidogenic effect is solely due to stimulated ACTH levels or whether a direct effect of AVP on the adrenal cortex is of physiological importance, has not been resolved.In canine isolated perfused adrenal glands, AVP alone or in combination with ACTH stimulated the secretion of cortisol (3,4). AVP infusions in dogs pretreated with dexamethasone only resulted in stimulation of glucocorticoids when ACTH was infused simultaneously. These results suggest that in the dog, AVP directly stimulates adrenal glucocorticoid production, provided that background levels of ACTH are present (5). Perfused rat isolated adrenals were stimulated to secrete corticosterone and aldosterone (6) by a bolus of as little as 10 fmol AVP. Superfused rat adrenal cells are stimulated by AVP to secrete aldosterone (7,8). AVP receptors (Vrtype) on rat glomerulosa cells have been de¬ scribed (7). In these cells, AVP stimulates calcium influx and phosphoinositide turnover (9).We attempted to answer the question whether AVP, besides stimulating ACTH secretion, also has a direct steroidogenic effect on the human adrenal. If AVP had a direct stimulatory effect on steroid secretion or would enhance the stimulatory effect of ACTH at a dose that stimulates ACTH secre¬ tion, the relationship between plasma ACTH and plasma steroid levels should be changed: the rela¬ tionship between elevated ACTH levels by ACTH injection and steroid secretion should differ from the relationship of ACTH stimulated by AVP infu¬ sion and steroid secretion. Subjects and MethodsAfter having given informed consent according to the Declaration of Helsinki, 15 normal men (between 21 and 32 years of age, body weights between 65 and 84 kg) participated in the study. All were non-smokers and on an unrestricted diet. On the study days at 12.00 h, they were given a light, standardized fat-free meal.

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Effects of angiotensin II and ACTH on normal and tumourous human adrenocortical cells

Cited by 10 publications

References 15 publications

Effects of β-Lipotropin, β-Endorphin, γ2-Melanotropin and Corticotropin on Steroid Production by Isolated Human Adrenocortical Cells

Effects of β-Lipotropin, β-Endorphin, γ2-Melanotropin and Corticotropin on Steroid Production by Isolated Human Adrenocortical Cells

CORTISOL PRODUCTION BY ALDOSTERONE‐PRODUCING ADENOMAS IN VITRO

Stimulation of steroid secretion by adrenocorticotropin injections and by arginine vasopressin infusions: no evidence for a direct stimulation of the human adrenal by arginine vasopressin

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