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Variable expression of the V1 vasopressin receptor modulates the phenotypic response of steroid-secreting adrenocortical tumors.

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TLDR
It is concluded that the vasopressin V1 receptor gene is expressed in normal and tumoral adrenocortical cells and high, and not ectopic, expression occurs in a minority of tumors that become directly responsive to vasoppressin stimulation tests.
Abstract
We studied the putative role of the vasopressin receptors in the phenotypic response of steroid-secreting adrenocortical tumors. A retrospective analysis of a series of 26 adrenocortical tumors responsible for Cushing’s syndrome (19 adenomas and 7 carcinomas) showed that vasopressin (10 IU, im, lysine vasopressin) induced an ACTH-independent cortisol response (arbitrarily defined as a cortisol rise above baseline of 30 ng/mL or more) in 7 cases (27%). In comparison, 68 of 90 patients with Cushing’s disease (76%) had a positive cortisol response. We then prospectively examined the expression of vasopressin receptor genes in adrenocortical tumors of recently operated patients (20 adenomas and 19 adrenocortical carcinomas). We used highly sensitive and specific quantitative RT-PCR techniques for each of the newly characterized human vasopressin receptors: V1, V2, and V3. The V1 messenger ribonucleic acid (mRNA) was detected in normal adrenal cortex and in all tumors. Its level varied widely between 2.0 × 102...

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Journal ArticleDOI

Cushing's syndrome

TL;DR: The current understanding of pathogenesis, clinical features, diagnostic, and differential diagnostic approaches, and diagnostic algorithms and recommendations for management of Cushing's syndrome are reviewed.
Journal ArticleDOI

Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome.

TL;DR: The mechanism by which cortisol is produced in adrenal Cushing's syndrome, when ACTH is suppressed, was previously unknown and was referred to as being “autonomous.” More recently several investigators have shown that some steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors.
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Leuprolide acetate therapy in luteinizing hormone--dependent Cushing's syndrome.

TL;DR: A woman with bilateral adrenal hyperplasia and corticotropin-independent Cushing's syndrome that was clinically manifested transiently during her pregnancies and became constant only after menopause is described, where the patient's cortisol secretion was stimulated by luteinizing hormone.
Journal ArticleDOI

ACTH-independent macronodular adrenal hyperplasia

TL;DR: The identification of aberrant receptors can offer a specific pharmacological approach to prevent progression and control abnormal steroidogenesis; alternatively, unilateral or bilateral adrenalectomy becomes the treatment of choice.
References
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Journal ArticleDOI

Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A

TL;DR: This work has identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls, and found that 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of theRET extracellular and transmembrane domains.
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Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor

TL;DR: Transgenic mice were created with cardiac-specific overexpression of the beta 2-adrenergic receptor that resulted in increased basal myocardial adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo, suggesting a potential gene therapy approach to this disease state.
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Molecular cloning of the receptor for human antidiuretic hormone.

TL;DR: The deduced amino-acid sequence of the receptor yields a hydropathy profile characteristic of receptors with seven putative transmembrane regions, which indicates that the ADH receptor is a member of the superfamily of G-protein-coupled receptors.
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Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the β2-adrenoceptor

TL;DR: It is shown that the β2-adrenoceptor ligand ICI-118,551 functions as an inverse agonist, providing evidence supporting the existence of inverse agonists and validating the two-state model of G-protein-coupled receptor activation.
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Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function.

TL;DR: Salivary cortisol measurements are an excellent index of plasma free cortisol concentrations that circumvent the physiological, pathological, and pharmacological changes due to corticosteroid-binding globulin alterations and offer a practical approach to assess pituitary-adrenal function.
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