Suramin Prevents Acth-Stimulated Corticosterone Release by Dispersed Adrenocortical Cells

Marzouk, H.; Zuyderwijk, J.; Uitterlinden, P.; Jong, Frank H. de; Lamberts, Steven W. J.

doi:10.1210/endo-126-1-666

Cited by 15 publications

(6 citation statements)

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“…Portions of the patient's adrenocortical tumours were transferred to the laboratory within 90 minutes after removal. The tissue was minced into small pieces and dissociated with collagenase (type I; Sigma Chemical Co., St. Louis, MO), as described previously (Marzouk et al ., 1990). Viability of the cells was determined by trypan blue exclusion, and was greater than 80%.…”

Section: Methodsmentioning

confidence: 99%

GIP‐dependent adrenal Cushing's syndrome with incomplete suppression of ACTH

Croughs

Zelissen

Vroonhoven

et al. 2000

Clinical Endocrinology

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ACTH-independent Cushing's syndrome may be due to the development of ectopic hormone receptors in adrenal tissue. Thus, in food-dependent Cushing's syndrome the adrenals aberrantly express receptors for gastric inhibitory polypeptide (GIP). We present the case of a 60-year-old woman with food-dependent Cushing's syndrome whose cortisol levels increased after stimulation with CRH. In this patient with Cushing's syndrome the finding of low basal plasma cortisol levels in the late night and early morning as well as a paradoxical rise of plasma cortisol during a 7-h infusion with dexamethasone (carried out without any restriction in food intake), suggested that cortisol production was stimulated at times of food intake. Hourly measurements of plasma cortisol for 48 h revealed prominent meal-related peaks. A plasma cortisol response, elicited by oral glucose administration, could be prevented by octreotide. Plasma ACTH was low or undetectable. CRH administration was followed by a ACTH response from 3 to 16 ng/l and a plasma cortisol response from 230 to 680 nmol/l. Octreotide treatment for nearly five months induced a partial clinical and biochemical remission. Total bilateral adrenalectomy was performed. The left adrenal was grossly enlarged (7 x 5.5 x 4 cm) and the right adrenal was slightly enlarged (6 x 4 x 1.8 cm). Microscopy revealed bilateral nodular hyperplasia. Cell suspensions of adrenal tissue from the patient did respond in a dose-dependent fashion to stimulation with GIP and were very sensitive to stimulation with synthetic ACTH1-24. However, CRH had no significant effect on cortisol production in vitro. Using RT-PCR amplification and cDNA hybridization, GIP receptor was found to be overexpressed in the left and right adrenal tissues from this patient as compared to adrenal tissues from a normal individual or from non GIP-dependent adrenal Cushing's syndrome. There was no evidence of presence of adrenal CRH receptors. Thus, in this patient with food-dependent Cushing's syndrome, the CRH-induced plasma ACTH and cortisol response is probably mediated by an incomplete suppression of the HPA axis as a result of the intermittent food-dependent nature of Cushing's syndrome.

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Section: Methodsmentioning

confidence: 99%

GIP‐dependent adrenal Cushing's syndrome with incomplete suppression of ACTH

Croughs

Zelissen

Vroonhoven

et al. 2000

Clinical Endocrinology

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“…According to another concept, suramin effects are primarily due to interference of the compound with the binding of hormones and growth factors to their receptors [2][3][4], The mechanism via which such an interaction should take place is however poorly understood. Several possibilities, such as a 'coating' of the cells with suramin, or extracellular binding of sura min to various ligands have been discussed [24]. Our re sults suggest that suramin does not induce a general de crease of ligand binding, but that its inhibitory effect seems to be epitope-specific.…”

Section: Discussionmentioning

confidence: 67%

Suramin Affects Human Peripheral Blood Mononuclear Cells in vitro: Inhibition of T Cell Growth and Modulation of Cytokine Secretion

Czernin

Gessl²,

Wilfing³

et al. 1993

Int Arch Allergy Immunol

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Suramin, a polyanionic compound, which has been in clinical use for the treatment of African trypanosomiasis for several decades, has recently been introduced in clinical oncology. Its effects on the immune system seemed therefore of interest. In the present study we tried to elucidate in vitro how suramin affected different functions of human peripheral blood mononuclear cells (PBMC). Suramin suppressed the proliferation of PBMC in response to various stimuli, including OKT3, phytohemagglutinin (PHA), phorbolmyristateacetate (PMA) and ionomycin, purified protein derivate of Mycobacterium tuberculosis (PPD) and antibodies against CD2. It also inhibited the binding of monoclonal antibodies to T cell surface antigens. This effect was not dependent on the isotype of the antibody, but seemed to be highly epitope-specific. Among a panel of antibodies against one antigen, only a few were affected by the compound. Whereas the binding of Leu3a and OKT3 was for instance fully suppressed by suramin, OKT4 and Leu4 binding was only slightly affected. Suramin also decreased the expression of T cell surface molecules such as CD2, CD25 and CD4 in preactivated PBMC and had pronounced effects on cytokine production. Interestingly the compound had adverse regulatory effects on different cytokines. Whereas the secretion of interferon-γ was completely suppressed by suramin, interleukin-2 (IL-2) and IL-4 production was stimulated. These results demonstrate that suramin affects T cell function in multiple different ways. This will have to be considered, when suramin is used in the treatment of cancer patients.

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“…Directly after laparoscopic removal, adrenal cortical tissue of the major part of the adrenals was minced into small pieces and dissociated with collagenase (type I; Sigma Chemical Co.), as described previously (5,6). Cell viability was determined by trypan blue staining and was more than 80%.…”

Section: Cell Preparation and Incubation Studiesmentioning

confidence: 99%

“…Subsequently, the cells were resuspended in incubation medium (DMEM with 0.2% BSA), and incubated with and without test substances during 2 or 24 h. These incubations were performed in quadruplicate using 500 000 cells/ml. After 2-h incubation, 0.5 ml distilled water was added to each tube, and the resulting suspension was stored at K20 8C until the measurement of hormone concentrations, as described previously (5). Cortisol concentrations were measured by a fluorescent immunoassay (Diagnostic Products Corp., Los Angeles, CA, USA).…”

Section: Cell Preparation and Incubation Studiesmentioning

confidence: 99%

Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome

Groot

Links²,

Themmen³

et al. 2010

European Journal of Endocrinology

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Objective: Aberrant adrenal expression of various hormone receptors has been identified in ACTHindependent macronodular adrenal hyperplasia (AIMAH) causing cortisol hypersecretion regulated by hormones other than ACTH. We aimed to determine aberrant expression of multiple hormone receptors in vivo and in vitro in adrenal tissue of a patient with AIMAH. Design: The design of the study includes clinical case description, and biochemical and immunohistochemical analysis to demonstrate aberrant expression of multiple hormone receptors in AIMAH. Methods: The subject of the study is a male diagnosed with Cushing's syndrome because of AIMAH. Directly after laparoscopic removal of the adrenals, adrenal tissue was incubated with and without test substances (ACTH, forskolin, arginine vasopressin (AVP), desmopressin, epinephrine, norepinephrine, purified human chorionic gonadotropin (hCG), metoclopramide and the combinations of AVP with ACTH, epinephrine and metoclopramide). LH/hCG-receptor (hCG-R) immunohistochemistry and RT-PCR analyses were performed to demonstrate aberrant expression of LH/hCG-R and V 1-3 -AVPR. Results: AIMAH was characterized by in vivo cortisol responsiveness to AVP and in vitro cortisol responses to AVP, hCG, epinephrine, and norepinephrine suggesting aberrant adrenal expression of the receptors for AVP (the V 1-3 -AVPRs), catecholamines (the b-AR), and LH (the LH/hCG-R). Incubation with combinations of AVP and ACTH and of AVP with epinephrine induced a stronger cortisol response compared with incubation with the individual agents. Moreover, we demonstrated adrenal V 1-3 -AVPR and LH/hCG-R expression. Conclusions: AIMAH tissue may simultaneously express multiple aberrant hormone receptors, and individual ligands may potentiate each other regarding cell proliferation and cortisol production.

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Suramin Prevents Acth-Stimulated Corticosterone Release by Dispersed Adrenocortical Cells

Cited by 15 publications

References 0 publications

GIP‐dependent adrenal Cushing's syndrome with incomplete suppression of ACTH

GIP‐dependent adrenal Cushing's syndrome with incomplete suppression of ACTH

Suramin Affects Human Peripheral Blood Mononuclear Cells in vitro: Inhibition of T Cell Growth and Modulation of Cytokine Secretion

Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome

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