PARTIAL CHARACTERISATION OF THE 5<sup>′</sup>FLANKING REGION OF THE HUMAN GIP RECEPTOR (GIPR) GENE

Baldacchino, Valérie; Oble, Sylvie; Hamet, Pavel; Tremblay, Johanne; Lacroix, André

doi:10.1081/erc-120016843

Cited by 3 publications

(3 citation statements)

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“…Furthermore, no mutations or polymorphisms have been encountered in the promoter region of the GIP-receptor gene in GIP-dependent CS [95]. Another mechanism by which the expression of membrane receptors may be altered is by disruption of trans-acting elements (transcription factors, co-activators, co-repressors) [96], as suggested by recent work [95,96]. This latter hypothesis is more interesting as it is consistent with the common co-expression of several aberrant receptors.…”

Section: Molecular Mechanisms Of Aberrant Receptorsmentioning

confidence: 77%

Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

2004

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In recent years, a novel understanding of the pathophysiology of adrenal Cushing's syndrome has emerged. The ectopic or aberrant expression of G-protein-coupled hormone receptors in the adrenal cortex was found to play a central role in the regulation of cortisol secretion in ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in some unilateral adrenal adenomas. Various aberrant receptors, functionally coupled to steroidogenesis, have been reported: GIP, vasopressin, beta-adrenergic, LH/hCG, and serotonin receptors have been best characterized, but angiotensin, leptin, glucagon, IL-1 and TSH receptors have also been described. The molecular mechanisms responsible for the aberrant expression of these receptors are currently unknown. One or many of these aberrant receptors are present in most cases of AIMAH and in some cases of adrenal adenomas with overt or sub-clinical secretion of cortisol. Clinical protocols to screen for such aberrant receptors have been developed and should be performed in all patients with AIMAH. The identification of such aberrant regulation of steroidogenesis in AIMAH provides the novel opportunity to treat some of these patients with pharmacological agents that either suppress the endogenous ligand or block the aberrant receptor, thus avoiding bilateral adrenalectomy.

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Section: Molecular Mechanisms Of Aberrant Receptorsmentioning

confidence: 77%

Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

2004

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“…Transcription binding motifs include a cAMP response element, an octamer-binding site and three SP1 sites; moreover, the region 200 bp upstream seems to repress GIPR transcription in cells that normally do not express this gene [38]. The human GIPR promoter is currently being characterized in our laboratory; its structure and functional elements in the putative proximal promoter are very similar to those of the rat GIPR promoter [39]. In this study, we examined if alterations in the regulatory regions of the GIPR gene underlie the adrenal overexpression of the GIPR gene in GIP-dependent CS.…”

Section: Introductionmentioning

confidence: 93%

Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing’s syndrome

Antonini

N’Diaye

Baldacchino

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…No mutations or polymorphisms were encountered in the promoter region of the GIP-receptor gene in GIP-dependent CS [114]. The identification of trans -acting elements implicated in tissue-specific expression of the hGIP receptor and their potential alterations are currently under way [115]. Alteration of trans -acting elements may be more likely and more consistent with the common co-expression of several aberrant receptors.…”

Section: Pathophysiologymentioning

confidence: 99%

Clinical and Subclinical ACTH-Independent Macronodular Adrenal Hyperplasia and Aberrant Hormone Receptors

Christopoulos

Bourdeau

Lacroix³

2005

Horm Res Paediatr

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ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a very rare cause of endogenous Cushing’s syndrome (CS). In this review, the clinical characteristics, the pathophysiology, and the management of AIMAH are described. AIMAH typically presents with overt CS, but subclinical oversecretion of cortisol has been increasingly described. The diagnosis is suspected by adrenal nodular enlargement on conventional imaging following the demonstration of ACTH-independent hypercortisolism. Final diagnosis is established by histological examination of the adrenal tissue. Bilateral adrenalectomy is the treatment of choice but unilateral adrenalectomy has been proposed in selected cases. In patients with subclinical CS, the decision to treat should be individualized. The pathophysiology of this condition has begun to be elucidated in recent years. Diverse aberrant membrane-bound receptors expressed in a non-mutated form in the adrenal gland have been found to be implicated in the regulation of steroidogenesis in AIMAH. When systematically screened, most patients with AIMAH and CS or subclinical CS exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. A protocol designed to screen patients for the presence of these aberrant receptors should be undertaken in all patients with AIMAH. The identification of these receptors provides the potential for novel pharmacological therapies by suppressing the endogenous ligands or blocking the receptor with specific antagonists.

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PARTIAL CHARACTERISATION OF THE 5^′FLANKING REGION OF THE HUMAN GIP RECEPTOR (GIPR) GENE

Cited by 3 publications

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Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing’s syndrome

Clinical and Subclinical ACTH-Independent Macronodular Adrenal Hyperplasia and Aberrant Hormone Receptors

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PARTIAL CHARACTERISATION OF THE 5′FLANKING REGION OF THE HUMAN GIP RECEPTOR (GIPR) GENE

Cited by 3 publications

References 0 publications

Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

Aberrant Expression of Hormone Receptors in Adrenal Cushing's Syndrome

Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing’s syndrome

Clinical and Subclinical ACTH-Independent Macronodular Adrenal Hyperplasia and Aberrant Hormone Receptors

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PARTIAL CHARACTERISATION OF THE 5^′FLANKING REGION OF THE HUMAN GIP RECEPTOR (GIPR) GENE