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.
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.


METHODS
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.
Machado
Marcio Carlos
MC
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, Brazil. marciocm@usp.br
Valeria de Sa
Sandra
S
Correa-Giannella
Maria Lucia
ML
Giorgi
Ricardo Rodrigues
RR
Pereira
Maria Adelaide Albergaria
MA
Cescato
Valter Angelo S
VA
Giannella-Neto
Daniel
D
Salgado
Luiz Roberto
LR
D000182:ACTH Syndrome, Ectopic / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D050034:Antidiuretic Agents / Q000008:administration & dosage; D002276:Carcinoid Tumor / Q000150:complications; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008175:Lung Neoplasms / Q000150:complications; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics*; D017483:Receptors, Vasopressin / Q000235:genetics; D013953:Thymus Neoplasms / Q000150:complications
D050034:Antidiuretic Agents; D009842:Oligopeptides; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D017483:Receptors, Vasopressin; C041048:growth hormone releasing hexapeptide; D000324:Adrenocorticotropic Hormone; D003894:Deamino Arginine Vasopressin; D006854:Hydrocortisone