Ghrelin Is Produced by and Directly Activates Corticotrope Cells from Adrenocorticotropin-Secreting Adenomas

Martínez-Fuentes, Antonio J.; Moreno-Fernández, Jesús; Vázquez-Martı́nez, Rafael; Durán-Prado, Mario; Riva, Andrés de la; Tena‐Sempere, Manuel; Diéguez, Carlos; Jiménez‐Reina, Luis; Webb, Susan M.; Pumar, A; Leal‐Cerro, Alfonso; Benito-López, Pedro; Malagón, Marı́a M.; Castaño, Justo P.

doi:10.1210/jc.2006-0235

Cited by 44 publications

(42 citation statements)

References 30 publications

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“…In patients with an ACTH-secreting tumour, ghrelin may further stimulate ACTH levels, and subsequently cortisol levels, through direct action on tumoral GHS-R (Correa-Silva et al, 2006). Ghrelin has been shown to act directly on corticotrope tumour cells derived from patients with Cushing's disease and this supports the suggestion of a cellular basis for the exaggerated ACTH response to ghrelin in Cushing's disease (Martinez-Fuentes et al, 2006). In addition, ghrelin has been shown in vitro to stimulate ACTH secretion by human ACTH-secreting pituitary adenomas (Pecori et al, 2007).…”

Section: Ghrelin and Cushing's Syndromementioning

confidence: 77%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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Section: Ghrelin and Cushing's Syndromementioning

confidence: 77%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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“…In published studies, there was no direct evidence of the stimulatory effect of the GHS-R antagonist on the release of glucocorticoids. The regulatory effect of ghrelin on glucocorticoids is well documented (11,12), although the infusion of ghrelin is not able to cause hypercortisolemia (11). In the present study, it seemed that the infusion of greater dosages of the GHS-R antagonist induced a GH-deficient condition, and subsequent increase in cortisol, similar to the study by Wagner and cols.…”

Section: Resultsmentioning

confidence: 99%

Effects of peptidic growth hormone secretagogue receptor (GHS-R) antagonist [D-Lys3] on some of serum hormonal and biochemical parameters in Wistar rat model

Shahryar

Lotfi

2014

Arq Bras Endocrinol Metab

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Objective: The present study investigated the effects of different dosages of a GHS-R antagonist on some serum hormonal (cortisol, T 3 and T 4 ) and biochemical parameters in a rat. Materials and methods: Thirty-six 60-day-old male rats were assigned to four treatments. [D--Lys3]-GHRP-6 solutions were infused via intraperitoneal injections. Blood was collected and analyzed. Results: The large dosages of a GHS-R antagonist (200 ng/kg BW) caused increases in cortisol, whereas no significant changes occurred when low dosages were injected. There were no significant changes in T 3 and T 4 following the administration of the GHS-R antagonist, but a considerable increase was observed in blood glucose levels of the groups (G50, G100, and G200 ng/kg BW). There was a significant increase in total protein when the greatest dose was administrated (G200 ng/kg BW). However, total cholesterol, triglycerides, and albumin showed no significant changes. Conclusions: Exogenous GHS-R antagonist can cause an increase in glucose and moderate increases in cortisol and total protein, yet it has no significant effect on T 3 and T 4 levels or on the concentrations of serum lipids. The effect of GHS-R antagonist is not completely adverse to the effects of ghrelin. Further molecular studies are necessary to identify the physiological effects of the peptidic GHS-R antagonist. Arq Bras Endocrinol Metab. 2014;58(3):288-91 Keywords Ghrelin receptor; GHS-R; GH-releasing; regulatory peptide; peripheral infusion RESUMO Objetivo: O presente estudo investigou os efeitos de diferentes doses do antagonista do GHS-R [D-Lys3] sobre alguns parâmetros hormonais (cortisol, T 3 e T 4 ) e bioquímicos em ratos. Materiais e métodos: Trinta e seis ratos machos com 60 dias de idade foram alocados para quatro tratamentos. Soluções de [D-Lys3]-GHRP-6 foram administradas por meio de injeções intraperitoneais e foram coletadas e analisadas amostras. Resultados: Doses altas de antagonista de GHS--R (200 ng/kg PC) levaram a aumento do cortisol, enquanto não houve diferença significativa quando foram injetadas doses baixas. Não houve alterações significativas em T 3 e T 4 depois da administração do antagonista do GHS-R, mas foi observado aumento considerável nos níveis de glicose sanguínea dos grupos (G50, G100 e G200 ng/kg PC). Houve aumento significativo na proteína total quando foi administrada a maior dose (G200 ng/kg PC), entretanto, não foram observadas alterações no colesterol total, nos triglicérides e na albumina. Conclusões: O antagonista do GHS-R exógeno pode causar aumento da glicose e aumento moderado do cortisol e proteína total, embora não haja efeitos significativos nos níveis de T 3 e T 4 ou na concentração de lipídios séricos. O efeito do antagonista de GHS-R não é completamente adverso aos efeitos da grelina. Devem ser feitos outros estudos moleculares para se identificar os efeitos fisiológicos do peptídeo antagonista do GHS-R. Arq Bras Endocrinol Metab. 2014;58(3):288-91 DescritoresReceptor da grelina, GHS-R, liberação de GH, peptídeo re...

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“…There is evidence of direct action of GHS on corticotrophic tumors, probably mediated by active GHS receptor -GHSR-1a. However, no direct effect was observed in a study with cultures of corticotrophic adenomas evaluated by intracellular calcium flow (28), while a direct action of ghrelin on two corticotrophinoma culture cells was recently demonstrated (29). In normal tissues, GHSR-1a is expressed mainly in the hypothalamus and pituitary (30).…”

Section: Discussionmentioning

confidence: 96%

“…Recently, a study demonstrated co-localization of ACTH and ghrelin in the same granules of two densely granulated corticotrophic tumors. The authors suggested that autocrine or paracrine action of ghrelin could be involved in the modulation of ACTH secretion by tumors (29).…”

Section: Discussionmentioning

confidence: 99%

Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing's syndrome patients

Machado

de²,

Côrrea-Giannella³

et al. 2008

European Journal of Endocrinology

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Objective: GH secretagogues (GHS) produce exaggerated ACTH and cortisol responses in Cushing's disease (CD) patients, attributable to their direct action on GH-releasing peptide receptor type 1a (GHSR-1a). However, there are no studies correlating the in vivo response to GHS and GHSR-1a mRNA expression in ACTH-dependent Cushing's syndrome (CS) patients. The aim of this study is to correlate the patterns of ACTH and cortisol response to GH-releasing peptide-6 (GHRP-6) to GHSR-1a expression in ACTH-dependent CS patients. Design: Prospective study in a tertiary referral hospital center. Fifteen CD patients and two ectopic ACTH syndrome (EAS) patients were studied. Methods: Tumor fragments were submitted to RNA extraction, and GHSR-1a expression was studied through real-time qPCR and compared with normal tissue samples. The patients were also submitted to desmopressin test and vasopressin receptor type 1B (AVPR1B) mRNA analysis by qPCR. Results: GHSR-1a expression was similar in normal pituitary samples and in corticotrophic tumor samples. GHSR-1a expression was higher in patients (CD and EAS) presenting in vivo response to GHRP-6. Higher expression of AVPR1B was observed in the EAS patients responsive to desmopressin, as well as in corticotrophic tumors, as compared with normal pituitary samples, but no correlation between AVPR1B expression and response to desmopressin was observed in the CD patients. Conclusions: Our results revealed a higher expression of GHSR-1a in the ACTH-dependent CS patients responsive to GHRP-6, suggesting an association between receptor gene expression and in vivo response to the secretagogue in both the CD and the EAS patients.European Journal of Endocrinology 158 605-613

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Ghrelin Is Produced by and Directly Activates Corticotrope Cells from Adrenocorticotropin-Secreting Adenomas

Cited by 44 publications

References 30 publications

Ghrelin in obesity and endocrine diseases

Ghrelin in obesity and endocrine diseases

Effects of peptidic growth hormone secretagogue receptor (GHS-R) antagonist [D-Lys3] on some of serum hormonal and biochemical parameters in Wistar rat model

Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing's syndrome patients

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