Multiple aberrant hormone receptors in Cushing's syndrome

Ghorayeb, Nada El; Bourdeau, Isabelle; Lacroix, André

doi:10.1530/eje-15-0200

Cited by 78 publications

(53 citation statements)

References 157 publications

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“…Peritumoral adrenal tissue from patient #1 did not express GIPR. Interestingly, as reported previously (11), concomitant aberrant expression of one or more G protein-coupled hormone receptors was detected in one adenoma (from patient #4) and in 3 hyperplasia samples (from patient #6, #10, and #11) in addition to GIPR (Supplemental Figure 2).…”

Section: Resultssupporting

confidence: 80%

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Lecoq¹,

Stratakis²,

Viengchareun³

et al. 2017

JCI Insight

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Section: Resultssupporting

confidence: 80%

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Lecoq¹,

Stratakis²,

Viengchareun³

et al. 2017

JCI Insight

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“…A transcriptome study identified increased mRNA of additional GPCRs; motilin, gamma-amino-butyric acid (GABBR1) and a-2 adrenergic (ADRA2A) receptors (Assie et al 2010). Responses to up to four stimuli has been reported in 50% of the patients indicating that multiple aberrant receptors may co-exist in each patient (Hofland et al 2013, El Ghorayeb et al 2015, St-Jean et al 2018. The molecular mechanisms leading to ectopic GPCRs expression in adrenal tissue are not known.…”

Section: Pathophysiologymentioning

confidence: 99%

Diagnosis and management of primary bilateral macronodular adrenal hyperplasia

Vassiliadi

Tsagarakis

2019

Endocrine-Related Cancer

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Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a highly heterogeneous entity. The incidental identification of an increasing number of cases has shifted its clinical expression from the rarely encountered severe forms, regarding both cortisol excess and adrenal enlargement, to mild forms of asymptomatic or oligosymptomatic cases with less impressive imaging phenotypes. Activation of cAMP/PKA pathway, either due to alterations of the different downstream signaling pathways or through aberrantly expressed G-protein-coupled receptors, relates to both cortisol secretion and adrenal growth. Germline ARMC5 mutations are a frequent genetic defect. The diagnostic approach consists of both imaging and hormonal characterization. Imaging characterization should be done separately for each lesion. Endocrine evaluation in cases with clinically overt Cushing’s syndrome (CS) is similar to that applied for all forms of CS. In incidentally detected PBMAH, hormonal evaluation includes testing for primary aldosteronism, pheochromocytoma and evaluation for autonomous cortisol secretion, using the 1 mg overnight dexamethasone suppression test. Midnight cortisol or 24-h urinary free cortisol may aid in establishing the degree of cortisol excess. In patients with hypercortisolism, ACTH levels should be measured in order to establish ACTH independency. At variance with other forms of CS, PBMAH may be characterized by a distinct pattern of inefficient steroidogenesis. The appropriate management of PBMAH remains controversial. Bilateral adrenalectomy results in lifetime steroid dependency and is better reserved only for patients with severe CS. Unilateral adrenalectomy might be considered in selected patients. In cases where the regulation of cortisol secretion is mediated by aberrant receptors there is some potential for medical therapy.

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“…In particular, 5-HT, produced by mast cells located in zona glomerulosa, is able to stimulate production of corticosteroids through a paracrine mechanism involving the 5-HT receptor type 4 (5-HT 4 ) expressed by adrenocortical cells (Contesse et al, 2002; Lefebvre et al, 2001, 1993, 1992). Moreover, overexpression of 5-HT 4 receptors has been reported in adrenal tumors responsible for hyperaldosteronism and hypercortisolism (Cushing’s syndrome) (Bertherat et al, 2005; Cartier et al, 2005; El Ghorayeb et al, 2015; Lefebvre et al, 2002). Deciphering the mechanism of action of 5-HT 4 receptors in adrenal is critical to understand the role of the serotonergic control of corticosteroid secretion in physiological and pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

Role of cAMP/PKA pathway and T-type calcium channels in the mechanism of action of serotonin in human adrenocortical cells

Louiset

Duparc

Lenglet

et al. 2017

Molecular and Cellular Endocrinology

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In human adrenal, serotonin (5-HT), produced by mast cells located in zona glomerulosa, stimulates production of corticosteroids through a paracrine mechanism involving the 5-HT receptor type 4 (5-HT4). The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT4 receptors in human adrenocortical cells. Our results show that 5-HT4 receptors are present in the outer adrenal cortex, both in glomerulosa and fasciculata zonae. In the zona glomerulosa. 5-HT4 receptor was detected both in immunopositive and immunonegative cells for 11β-hydroxylase, an enzyme involved in cortisol synthesis. The data demonstrate that 5-HT4 receptors are positively coupled to adenylyl cyclases and cAMP-dependent protein kinases (PKA). The activation of the cAMP-PKA pathway is associated with calcium influx through T-type calcium channels. Both the adenylyl cyclase/PKA pathway and the calcium influx are involved in 5-HT-induced cortisol secretion.

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Multiple aberrant hormone receptors in Cushing's syndrome

Cited by 78 publications

References 157 publications

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Diagnosis and management of primary bilateral macronodular adrenal hyperplasia

Role of cAMP/PKA pathway and T-type calcium channels in the mechanism of action of serotonin in human adrenocortical cells

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