Abnormal hormone responses of an adrenocortical cancer adenyl cyclase

Schorr, Immanuel; Ney, Robert L.

doi:10.1172/jci106608

Cited by 101 publications

(39 citation statements)

References 9 publications

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“…Adenylyl cyclase is normally coupled exclusively to ACTH in normal adrenocortical tissue, but some early studies found that it responded to epinephrine and norepinephrine in adrenocortical cancer tissue. 22,32 Alpha-2A adrenergic receptors were identified in cell cultures from ACTH-independent macronodular adrenal hyperplasia (AIMAH). 33 Beta-2 adrenergic receptors were identified in human adrenocortical cortisol-producing adenomas 34,35 or hyperplasia.…”

Section: Epinephrine and Norepinephrinementioning

confidence: 99%

“…However, some cases of Cushing's syndrome result from cortisol-secreting adrenal tumors, most of which are benign adrenocortical adenomas, adrenal cancer, or precancerous nodular adrenal hyperplasia 21 and some cases in an ACTH-independent manner. ACTHindependent stimulation of cortisol production was discovered in 1971, 22 with more reports in recent years. This review attempts to summarize in vivo case reports and the studies with cell cultures in vitro on hypercortisolism.…”

Section: Introductionmentioning

confidence: 99%

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ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

Li¹,

Hanna²

2016

Cell Communication Insights

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Cortisol production is normally under the regulation of adrenocorticotropic hormone (ACTH). Hypercortisolism or Cushing's syndrome, characterized by excessive cortisol levels, may be caused by ACTH-independent mechanisms. The present work aims to review the current knowledge on ACTH-independent mechanisms through aberrant expression of hormone receptors in adrenal tumors and adrenocortical hyperplasia. In particular, the effects of epinephrine, norepinephrine, serotonin, arginine vasopressin, and gastric inhibitory polypeptide are discussed.KEY WORDS: hypercorticism, adrenal tumors, adrenocortical hyperplasia, Cushing's syndrome, ACTH-independent CITATION: liu and hanna. aCth-independent hypercorticism in adrenal tumors and adrenocortical hyperplasia.

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Section: Epinephrine and Norepinephrinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

Li¹,

Hanna²

2016

Cell Communication Insights

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“…It has long been known that tumor cells may express GPCRs in an aberrant fashion (8). In an unbiased approach we investigated gene expression levels of all known GPCRs in a series of human SCLC, NSCLC, and normal lung RNA samples.…”

Section: Gpr19 Mrna Expression Is High In Sclc Patient Samples and Cementioning

confidence: 99%

“…Their uncontrolled exploitation-mostly seen by overexpression of GPCRs-could in turn contribute to the malignant transformation of cells (6,7). It has long been known that illegitimate expression of GPCRs occurs in tumor cells (8) and an involvement in cell-cycle control has been shown for several GPCRs and GPCR-associated proteins. For instance, H4 histamine receptors mediate a reversible cell-cycle arrest in growth factor-induced hematopoietic progenitor cells (9) and GPCR kinase 5 was assigned an essential role in the regulation of prostate tumor growth by affecting cell-cycle control (10).…”

Section: Introductionmentioning

confidence: 99%

Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G2–M Cell-Cycle Progression

Kastner

Voss

Keuerleber

et al. 2012

Molecular Cancer Research

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It has long been known that G protein-coupled receptors (GPCR) are subject to illegitimate expression in tumor cells. Presumably, hijacking the normal physiologic functions of GPCRs contributes to all biologic capabilities acquired during tumorigenesis. Here, we searched for GPCRs that were expressed in lung cancer: the mRNA encoding orphan G protein-coupled receptor 19 (GPR19) was found frequently overexpressed in tissue samples obtained from patients with small cell lung cancer. Several observations indicate that overexpression of Gpr19 confers a specific advantage to lung cancer cells by accelerating transition through the cellcycle. (i) Knockdown of Gpr19 mRNA by RNA interference reduced cell growth of human lung cancer cell lines. (ii) Cell-cycle progression through G 2 -M-phase was impaired in cells transfected with siRNAs directed against Gpr19 and this was associated with increased protein levels of cyclin B1 and phosphorylated histone H3. (iii) The expression levels of Gpr19 mRNA varied along the cell-cycle with a peak observed in S-phase. (iv) The putative control of Gpr19 expression by E2F transcription factors was verified by chromatin immunoprecipitation: antibodies directed against E2F-1 to -4 allowed for the recovery of the Gpr19 promoter. (v) Removal of E2F binding sites in the Gpr19 promoter diminished the expression of a luciferase reporter.

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“…This concept was first introduced by Ney and colleagues (29), who demonstrated in vitro that cAMP and corticosterone production in rat adrenocortical carcinoma cells were stimulated by non-ACTH hormones, such as catecholamines, TSH, FSH, LH, and prostaglandin E1. This hypothesis was later validated in humans by additional in vitro and in vivo studies (2,30).…”

Section: Aberrant Hormone Receptorsmentioning

confidence: 99%

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

Costa

Lacroix

2007

Arq Bras Endocrinol Metab

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ACTH-Independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome (CS), in which clinical features usually become apparent only after several decades of life. This form of adrenal hyperplasia typically produces excess cortisol with overt or subclinical CS, but concurrent secretion of mineralocorticoids or sexual steroids can also occur. The diagnosis is suspected by bilateral adrenal nodules larger than 1 cm on incidental imaging studies or following the demonstration of ACTH-independent hormonal hypersecretion. The pathophysiology of this entity is heterogeneous and has been intensely explored in recent years. Several G-protein coupled receptors aberrantly expressed in the adrenal cortex have been implicated in the regulation of steroidogenesis and in the initial cell proliferation in AIMAH. Several familial cases of AIMAH have been recently described with the same pattern of aberrant hormone receptors in all affected members of the family. It is probable that additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition over time in the various nodules; other mechanisms, as Gsp or ACTH receptor mutations and paracrine adrenal hormonal secretion have been rarely identified as the molecular mechanism in some cases. When systematically screened, most patients with AIMAH exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. The identification of these receptors creates the possibility of a specific pharmacological treatment isolated or associated with adrenalectomy. A hiperplasia adrenal macronodular independente de ACTH (AIMAH) é uma causa rara de síndrome de Cushing (SC) endógena, na qual alguns aspectos clínicos só se tornam evidentes depois de várias décadas de vida. Esta forma de hiperplasia adrenal caracteristicamente produz excesso de cortisol resultando na síndrome de Cushing franca ou subclínica, embora a secreção concomitante de mineralocorticóide, estrógeno e andrógenos também possa ocorrer. A suspeita diagnóstica é feita pela presença de nódulos adrenais bilaterais maiores que 1 cm, como achado incidental em exames de imagem ou pela demonstração de hipersecreção hormonal independente de ACTH. A fisiopatologia desta doença é heterogênea e tem sido intensamente estudada nos últimos anos. Vários receptores acoplados à proteína G, com expressão aberrante no córtex adrenal, têm sido implicados na regulação da esteroidogênese e no início da proliferação celular que ocorre na AIMAH. Diversos casos familiais de AIMAH foram recentemente descritos, e um mesmo padrão de expressão anormal dos receptores aberrantes foi observado em todos os membros afetados das famílias investigadas. Ao longo do tempo, é provável que ocorram, nos nódulos, eventos genéticos adicionais relacionados à regulação do ciclo celular, adesão e fatores de transcrição. Outros mecanismos moleculares, como mutações nos genes da proteína Gsα e do receptor de ACTH, ou ...

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Abnormal hormone responses of an adrenocortical cancer adenyl cyclase

Cited by 101 publications

References 9 publications

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

ACTH-Independent Hypercorticism in Adrenal Tumors and Adrenocortical Hyperplasia

Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G2–M Cell-Cycle Progression

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

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