In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome

1995 ◽  
Vol 132 (3) ◽  
pp. 292-299 ◽  
Author(s):  
Yoshihiro Nishi ◽  
Masafumi Haji ◽  
Ryoichi Takayanagi ◽  
Toshihiko Yanase ◽  
Shoichiro Ikuyama ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cushing’S Syndrome ◽  
General Circulation ◽  
Adrenal Glands ◽  
Cushing's Syndrome ◽  
Secretion Rate ◽  
Pathological Conditions ◽  
Adrenocortical Adenomas

Nishi Y, Haji M, Takayanagi R, Yanase T, Ikuyama S, Nawata H. In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome. Eur J Endocrinol 1995;132:292–9. ISSN 0804–4643 To clarify whether adrenal gland secretes inhibin in vivo in physiological or pathological conditions, we measured the levels of inhibin-like immunoreactivity (inhibin-LI) in adrenal veins (A-vein) and compared them with those in inferior vena cava (IVC) using blood samples obtained at catheterization of adrenal vein in the patients with adrenal adenoma manifesting Cushing's syndrome (Cs), aldosterone-producing adenoma, clinically non-functioning adenoma and normal adrenal gland. The tumor sides of A-veins in the patients with adenomas and also both sides of A-veins in subjects with normal adrenal glands showed significantly higher contents of inhibin-LI than their IVC. When the inhibin-LI secretion rate from adrenal gland was estimated by the difference between the levels of A-vein (tumor side) and IVC, Cs adenomas showed the highest secretion rate. Similarly, the tissue inhibin-LI content and the basal secretion rate of inhibit-LI from primary cultured cells were the highest in Cs adenomas. These findings indicated that normal adrenal glands and adrenocortical adenomas produced and secreted inhibin-LI into the general circulation in vivo and Cs adenomas have relatively high capacity for secreting inhibin-LI, and the present study provided the first in vivo evidence for adrenal inhibin-LI production in pathological conditions Yoshihiro Nishi, Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812, Japan

STUDIES ON THE IN VITRO PRODUCTION OF CORTICOSTEROIDS BY ADRENAL GLANDS FROM NORMOTENSIVE INDIVIDUALS AND HYPERTENSIVE PATIENTS

1962 ◽  
Vol 40 (1) ◽  
pp. 285-301 ◽  
Author(s):  
Jean Davignon ◽  
Erich Koiw ◽  
Wojciech Nowaczynski ◽  
Gilles Tremblay ◽  
Jacques Genest
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Glands ◽  
Cushing's Syndrome ◽  
The Other ◽  
Malignant Hypertension ◽  
Unit Weight ◽  
Chromatographic Technique ◽  
Acth Stimulation ◽  
The Mean

The production of aldosterone and other corticosteroids by adrenal glands surgically removed from 5 normotensive subjects with renal disease of various types, 11 patients with arterial hypertension, and 2 with Cushing's syndrome was investigated in vitro by the incubation chromatographic technique. The rate of steroid formation per unit weight of tissue was markedly lower in severe and malignant hypertension and slightly higher in benign hypertension as compared with the rate in normotensive controls. The amount of steroid released varied widely from one gland to the other and showed marked overlapping between the various groups; these variations were most prominent in benign hypertension, less in the normotensive group, and least evident in severe and malignant hypertension. The response of steroidogenesis to ACTH stimulation in vitro was slightly reduced in severe and malignant hypertension. The mean output of aldosterone by adrenal glands from hypertensives was slightly above the mean value obtained with normotensive control glands. The percentage of aldosterone formation in respect to total steroid production was roughly correlated with the severity of hypertension. In four hyperplastic adrenals obtained from two cases of Cushing's syndrome, the in vitro formation of steroids per unit weight of tissue and the response to ACTH did not differ significantly from that found in glands obtained from the other patients under study. The value of in vitro studies for the assessment of the functional capacity of the adrenal cortex is discussed.

IN VITRO AND IN VIVO EFFECT OF GROWTH HORMONE ON ALDOSTERONE SECRETION

1960 ◽  
Vol 38 (1) ◽  
pp. 1069-1075
Author(s):  
O. J. Lucis ◽  
E. H. Venning
Keyword(s):  
Growth Hormone ◽  
Adrenal Gland ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Hypophysectomized Rats

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.

scholarly journals TXNIP is highly regulated in bone biopsies from patients with endogenous Cushing's syndrome and related to bone turnover

2012 ◽  
Vol 166 (6) ◽  
pp. 1039-1048 ◽  
Author(s):  
Tove Lekva ◽  
Thor Ueland ◽  
Hege Bøyum ◽  
Johan Arild Evang ◽  
Kristin Godang ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Cushing’S Syndrome ◽  
Bone Cells ◽  
Cushing's Syndrome ◽  
Gene Encoding ◽  
Osteoclast Activity ◽  
Bone Biopsies ◽  
Before And After

ObjectivePatients with endogenous Cushing's Syndrome (CS), as long-time treated patients with exogenous glucocorticoids (GCs), have severe systemic manifestations including secondary osteoporosis and low-energy fractures. The aim of the present study was to investigate the functional role ofTXNIPin bone with focus on osteoblast (OB) differentiation and OB-mediated osteoclast activity and functionin vitro.Design and methodsNine bone biopsies from CS before and after surgical treatment were screened for expressional candidate genes. Microarray analyses revealed that the gene encodingTXNIPranked among the most upregulated genes. Subsequentin vitroandin vivostudies were performed.ResultsWe found thatTXNIPgene in bone is downregulated in CS following surgical treatment. Furthermore, ourin vivodata indicate novel associations between thioredoxin andTXNIP. Ourin vitrostudies showed that silencingTXNIPin OBs was followed by increased differentiation and expression and secretion of osteocalcin as well as enhanced activity of alkaline phosphatase. Moreover, treating osteoclasts with silenced TXNIP OB media showed an increased osteoclast activity.ConclusionsTXNIPexpression in bone is highly regulated during the treatment of active CS, and by GC in bone cellsin vitro. Our data indicate that TXNIP may mediate some of the detrimental effects of GC on OB function as well as modulate OB-mediated osteoclastogenesis by regulating the OPG/RANKL ratio.

scholarly journals cAMP signaling in cortisol-producing adrenal adenoma

2015 ◽  
Vol 173 (4) ◽  
pp. M99-M106 ◽  
Author(s):  
Davide Calebiro ◽  
Guido Di Dalmazi ◽  
Kerstin Bathon ◽  
Cristina L Ronchi ◽  
Felix Beuschlein
Keyword(s):  
Signaling Pathway ◽  
Cushing’S Syndrome ◽  
Cell Function ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Camp Signaling ◽  
Common Finding ◽  
Adrenocortical Adenomas ◽  
Camp Signaling Pathway

The cAMP signaling pathway is one of the major players in the regulation of growth and hormonal secretion in adrenocortical cells. Although its role in the pathogenesis of adrenocortical hyperplasia associated with Cushing's syndrome has been clarified, a clear involvement of the cAMP signaling pathway and of one of its major downstream effectors, the protein kinase A (PKA), in sporadic adrenocortical adenomas remained elusive until recently. During the last year, a report by our group and three additional independent groups showed that somatic mutations of PRKACA, the gene coding for the catalytic subunit α of PKA, are a common genetic alteration in patients with Cushing's syndrome due to adrenal adenomas, occurring in 35–65% of the patients. In vitro studies revealed that those mutations are able to disrupt the association between catalytic and regulatory subunits of PKA, leading to a cAMP-independent activity of the enzyme. Despite somatic PRKACA mutations being a common finding in patients with clinically manifest Cushing's syndrome, the pathogenesis of adrenocortical adenomas associated with subclinical hypercortisolism seems to rely on a different molecular background. In this review, the role of cAMP/PKA signaling in the regulation of adrenocortical cell function and its alterations in cortisol-producing adrenocortical adenomas will be summarized, with particular focus on recent developments.

CONCURRENT 3β-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY IN ADRENAL AND SCLEROCYSTIC OVARY

1965 ◽  
Vol 48 (3) ◽  
pp. 392-412 ◽  
Author(s):  
Leonard R. Axelrod ◽  
Joseph W. Goldzieher ◽  
S. David Ross
Keyword(s):  
Cushing’S Syndrome ◽  
Dehydrogenase Deficiency ◽  
Clinical Manifestations ◽  
Regulatory System ◽  
Hydroxysteroid Dehydrogenase ◽  
Cushing's Syndrome ◽  
Hypothalamic Pituitary Adrenal ◽  
Relative Deficiency

ABSTRACT In vivo and in vitro studies were performed in a virilized patient with enlarged sclerocystic ovaries, in whom urinary corticoid excretion was not suppressed by dexamethasone. Both ovarian and adrenal tissues were incubated with 5-pregnenolone-4-14C and the metabolites isolated and definitively identified. Both tissues showed a relative deficiency of 3β-hydroxysteroid dehydrogenase. The ovarian aromatizing mechanism was intact. 5-Androstene-3β,17β-diol was the major adrenal biosynthetic product, and its metabolites were identified in the urine. The abnormality of the hypothalamic-pituitary-adrenal regulatory system resembled that seen in Cushing's syndrome, but the clinical manifestations were altered by the steroid enzyme abnormality.

scholarly journals Cushing’s Syndrome in a Patient with Bilateral Macronodular Adrenal Hyperplasia Responding to Cisapride: An in Vivo and in Vitro Study

2003 ◽  
Vol 88 (10) ◽  
pp. 4616-4622 ◽  
Author(s):  
Massimo Mannelli ◽  
Pietro Ferruzzi ◽  
Paola Luciani ◽  
Clara Crescioli ◽  
Lisa Buci ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
In Vitro Study ◽  
Cushing's Syndrome ◽  
Vitro Study ◽  
Adrenal Hyperplasia

scholarly journals IN VIVO AND IN VITRO STUDIES OF ADRENAL SECRETIONS IN CUSHING'S SYNDROME AND PRIMARY ALDOSTERONISM*

1963 ◽  
Vol 42 (4) ◽  
pp. 516-524 ◽  
Author(s):  
Edward G. Biglieri ◽  
Satoshi Hane ◽  
Paul E. Slaton ◽  
Peter H. Forsham
Keyword(s):  
Cushing’S Syndrome ◽  
Primary Aldosteronism ◽  
Cushing's Syndrome ◽  
In Vitro Studies

scholarly journals A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing’s Syndrome

2016 ◽  
Vol 101 (11) ◽  
pp. 4290-4297 ◽  
Author(s):  
Anli Tong ◽  
Guanghua Liu ◽  
Fen Wang ◽  
Jun Jiang ◽  
Zhaoli Yan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Channel Blockers ◽  
Type Iii ◽  
Adrenal Hormone ◽  
Familial Hyperaldosteronism ◽  
Bilateral Adrenal Hyperplasia

Context: To date, all the familial hyperaldosteronism type III (FH-III) patients reported presenting with typical primary aldosteronism (PA), without showing other adrenal hormone abnormalities. Objective: This study characterized a novel phenotype of FH-III and explored the possible pathogenesis. Patients and Methods: A male patient presented with severe hypertension and hypokalemia at the age of 2 years and developed Cushing’s syndrome at 20 years. He was diagnosed with PA and Cushing’s syndrome on the basis of typical biochemical findings. He had massive bilateral adrenal hyperplasia and underwent left adrenalectomy. KCNJ5 was sequenced, and secretion of aldosterone and cortisol were observed both in vivo and in vitro. Results: A heterozygous germline p.Glu145Gln mutation of KCNJ5 was identified. ARMC5, PRKAR1A, PDE8B, PDE11A, and PRKACA genes and β-catenin, P53 immunoactivity were normal in the adrenal. CYP11B2 was highly expressed, whereas mRNA expression of CYP11B1, CYP17A1, and STAR was relatively low in the hyperplastic adrenal, compared with normal adrenal cortex and other adrenal diseases. In the primary cell culture of the resected hyperplastic adrenal, verapamil and nifedipine, two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol and the mRNA expression of CYP11B1, CYP11B2, CYP17A1, and STAR. Conclusions: We presented the first FH-III patient who had both severe PA and Cushing’s syndrome. Hypersecretion of cortisol might be ascribed to overly large size of the hyperplastic adrenal because CYP11B1 expression was relatively low in his adrenal. Like aldosterone, synthesis and secretion of cortisol in the mutant adrenal may be mediated by voltage-gated Ca2+ channels.

Incidentally discovered ACTH-dependent adrenal adenoma presenting as 'Pre-Cushing's syndrome'

1986 ◽  
Vol 111 (1) ◽  
pp. 89-92 ◽  
Author(s):  
U. Bogner ◽  
U. Eggens ◽  
J. Hensen ◽  
W. Oelkers
Keyword(s):  
Cushing’S Syndrome ◽  
Adrenal Mass ◽  
Adrenal Adenoma ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Adrenal Tumour ◽  
Urinary Cortisol

Abstract. An adrenal tumour was incidentally discovered with no clinical signs of Cushing's syndrome. The endocrine evaluation revealed the unique hormonal constellation of an increased urinary cortisol excretion rate, unequivocal suppressibility of plasma and urinary cortisol by dexamethasone, but only to a residual level in the low normal range which probably reflected ACTH-independent 'autonomous' cortisol secretion. After removal of the adrenal mass, urinary cortisol secretion and dexamethasone suppressibility were normalized. In vitro, the tumour cells were as sensitive towards ACTH as 'normal' human adrenal cells, but showed a reduced cortisol production rate per cell. We suppose that the adrenal mass participated in the diurnal rhythm of ACTH-mediated cortisol secretion in vivo, which resulted in an increased cortisol secretion. During the night, when ACTH levels were low, the cortisol production decreased and the hormone levels were probably too low to suppress ACTH. We regard the hormonal findings in our patients as 'Pre-Cushing's syndrome', although the absence of clinical features of Cushing's syndrome remains unclear. We suggest that every patient with an incidentally discovered adrenal mass should have an endocrinological evaluation because the results may help to decide whether or not the adrenal tumour should be removed.

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