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.

Abstract

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.

• Authors: Marcio Carlos Machado, Sandra Valeria de Sa, Maria Lucia Correa-Giannella, Ricardo Rodrigues Giorgi, Maria Adelaide Albergaria Pereira, Valter Angelo S Cescato, Daniel Giannella-Neto, Luiz Roberto Salgado
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 158 Issue 5 Pg. 605-13 (May 2008) ISSN: 1479-683X [Electronic] England
• PMID: 18426818 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antidiuretic Agents
• Oligopeptides
• RNA, Messenger
• Receptors, Ghrelin
• Receptors, Vasopressin
• growth hormone releasing hexapeptide
• Adrenocorticotropic Hormone
• Deamino Arginine Vasopressin
• Hydrocortisone

Topics

• ACTH Syndrome, Ectopic (diagnosis, etiology, metabolism)
• Adolescent
• Adrenocorticotropic Hormone (blood)
• Adult
• Antidiuretic Agents (administration & dosage)
• Carcinoid Tumor (complications)
• Cushing Syndrome (diagnosis, etiology, metabolism)
• Deamino Arginine Vasopressin (administration & dosage)
• Diagnosis, Differential
• Female
• Humans
• Hydrocortisone (blood)
• Lung Neoplasms (complications)
• Male
• Middle Aged
• Oligopeptides (administration & dosage)
• Prospective Studies
• RNA, Messenger (metabolism)
• Receptors, Ghrelin (genetics)
• Receptors, Vasopressin (genetics)
• Thymus Neoplasms (complications)