125I-Tyr0-hCRH Labelling characteristics of corticotropin-releasing hormone receptors: differences between normal and adenomatous corticotrophs

Abs, R.

doi:10.1016/s0197-0186(96)00102-7

Cited by 10 publications

(4 citation statements)

References 20 publications

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“…Apparently conflicting data were presented by a recent study (43), showing that in adenomatous corticotrophs CRF-R expression is disturbed with respect to both number and distribution. Accordingly, the authors demonstrated a decrease in the number of CRF binding sites in adenomatous pituitaries that was associated with a redistribution of binding sites to the cell periphery.…”

Section: Discussionmentioning

confidence: 89%

Mutation and Expression Analysis of Corticotropin-Releasing Factor 1 Receptor in Adrenocorticotropin-Secreting Pituitary Adenomas1

Dieterich

Gundelfinger²,

Lüdecke

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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The present study was designed to investigate a possible role of CRF 1 receptors (CRF 1 -R) in the pathogenesis of Cushing's disease. ACTH-secreting pituitary adenomas and nonsecreting pituitary adenomas have been analyzed for mutations in the CRF 1 -R gene by PCR and sequencing and been compared with the sequences of normal anterior pituitaries. No mutations affecting the CRF 1 -R protein have been found in all tumors analyzed. However, we found a significant overexpression of the CRF 1 -R messenger RNA in ACTH-secreting pituitary adenomas vs. inactive adenomas and normal pituitaries. We conclude that mutations of the CRF 1 -R are unlikely to be involved in Cushing's disease. We suggest that the overexpression of the CRF 1 -R messenger RNA may be related to a disturbed receptor regulation in ACTH-secreting pituitary adenomas. (J Clin Endocrinol Metab 83: 3327-3331, 1998)

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Section: Discussionmentioning

confidence: 89%

Mutation and Expression Analysis of Corticotropin-Releasing Factor 1 Receptor in Adrenocorticotropin-Secreting Pituitary Adenomas1

Dieterich

Gundelfinger²,

Lüdecke

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…The CRH - R1 receptor was expressed at variable levels among specimens, confirming and extending findings reported on a small number of adenomas [ 5 , 6 , 36 ]. In detail, receptor binding studies had been performed in 5 adenomas, and considerable differences in the percentage of 125 I-hCRH-labeled cells among specimens had been observed [ 37 ]. The CRH - R1 gene itself reportedly was not mutated in ACTH-secreting pituitary adenomas [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas

et al. 2016

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ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing’s disease pathophysiology.Electronic supplementary materialThe online version of this article (doi:10.1007/s12020-016-0990-x) contains supplementary material, which is available to authorized users.

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“…In a study that determined 125 I‐Tyr o ‐hCRH binding on corticotroph tumours and normal pituitary, Abs et al. 42 revealed abnormal binding of CRH to some adenomatous corticotrophs. In our study, the expression of tumour CRHR was not associated with either ACTH increment percentage or netAUC of ACTH in CRH stimulation test.…”

Section: Discussionmentioning

confidence: 99%

“…An in vitro study showed that sensitivity of corticotrophinoma cells to CRH was low in some cases, while cAMP could stimulate ACTH secretion in all cases, suggesting a decrease in CRHR number and/or affinity. 41 In a study that determined 125 I-Tyr o -hCRH binding on corticotroph tumours and normal pituitary, Abs et al 42 revealed abnormal binding of CRH to some adenomatous corticotrophs. In our study, the expression of tumour CRHR was not associated with either ACTH increment percentage or netAUC of ACTH in CRH stimulation test.…”

Section: Discussionmentioning

confidence: 99%

Plasma corticotrophin response to desmopressin in patients with Cushing’s disease correlates with the expression of vasopressin receptor 2, but not with that of vasopressin receptor 1 or 3, in their pituitary tumours

Wang

Tang²,

Yen

et al. 2012

Clinical Endocrinology

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125I-Tyr0-hCRH Labelling characteristics of corticotropin-releasing hormone receptors: differences between normal and adenomatous corticotrophs

Cited by 10 publications

References 20 publications

Mutation and Expression Analysis of Corticotropin-Releasing Factor 1 Receptor in Adrenocorticotropin-Secreting Pituitary Adenomas1

Mutation and Expression Analysis of Corticotropin-Releasing Factor 1 Receptor in Adrenocorticotropin-Secreting Pituitary Adenomas1

Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas

Plasma corticotrophin response to desmopressin in patients with Cushing’s disease correlates with the expression of vasopressin receptor 2, but not with that of vasopressin receptor 1 or 3, in their pituitary tumours

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