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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

¹ Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo School of Medicine, Avenida Dr Eneas de Carvalho Aguiar, 155, 8th floor, Cerqueira Cesar, 05403-060 Sao Paulo, SP, Brazil² Neuroendocrine Unit, Service of Endocrinology and Metabolism, Hospital de Clinicas, Federal University of Parana (SEMPR), Avenida Agostinho Leao Junior, 285, Alto da Gloria, Curitiba 80030-110 PR, Brazil³ Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of Sao Paulo School of Medicine, Avenida Dr. Arnaldo 455, 4307, Cerqueira Cesar 01246-903 Sao Paulo, SP, Brazil⁴ Divisions of Endocrinology and Metabolism University of Sao Paulo School of Medicine, Avenida Dr Eneas de Carvalho Aguiar,155, 8th floor, Cerqueira Cesar, Sao Paulo 05403-060, Brazil⁵ Division of Neurosurgery, University of Sao Paulo School of Medicine, Rua Ovidio Pires de Campos, 785, Cerqueira Cesar, 01060-970 Sao Paulo, Brazil

(Correspondence should be addressed to M C Machado who is now at Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo School of Medicine, Av. Dr Eneas de Carvalho Aguiar #155, 8th floor, Cerqueira Cesar, Sao Paulo 05403-060, SP, Brazil; Email: marciocm{at}usp.br)

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.