Zakariae Bram1, Paraskevi Xekouki, Estelle Louiset, Meg F Keil, Dimitrios Avgeropoulos, Christoforos Giatzakis, Maria Nesterova, Ninet Sinaii, Leo J Hofland, Rabia Cherqaoui, Hervé Lefebvre, Constantine A Stratakis. 1. INSERM Unité 982 (Z.B., E.L., H.L.), Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Rouen, France; Section on Endocrinology and Genetics (P.X., D.A., C.G., M.N., R.C., C.A.S.), Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Pediatric Endocrinology Inter-Institute Training Program (M.F.K., C.A.S.), National Institute of Child Health and Human Development, National Institutes of Health, and Clinical Center (N.S.), National Institutes of Health, Bethesda, Maryland 20892; Erasmus Medical Center (L.J.H.), 3015 GE Rotterdam, The Netherlands; and Department of Endocrinology (H.L.), Institute for Research and Innovation in Biomedicine, University Hospital of Rouen, 76031 Rouen, France.
Abstract
CONTEXT: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. OBJECTIVES: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease (PPNAD) tissues and to test the effect of a single injection of 100 μg of the SST analog octreotide on cortisol secretion in patients with PPNAD. SETTING AND DESIGN: The study was conducted at an academic research laboratory and clinical research center. Expression of SSTRs was examined in 26 PPNAD tissues and the immortalized PPNAD cell line CAR47. Ten subjects with PPNAD underwent a randomized, single-blind, crossover study of their cortisol secretion every 30 minutes over 12 hours (6:00 pm to 6:00 am) before and after the midnight administration of octreotide 100 μg sc. METHODS:SSTRs expression was investigated by quantitative PCR and immunohistochemistry. The CAR47 and primary cell lines were studied in vitro. The data of the 10 patients were analyzed before and after the administration of octreotide. RESULTS: All SSTRs, especially SSTR1-3, were expressed in PPNAD at significantly higher levels than in normal adrenal. SST was found to differentially regulate expression of its own receptors in the CAR47 cell line. However, the administration of octreotide to patients with PPNAD did not significantly affect cortisol secretion. CONCLUSIONS: SSTRs are overexpressed in PPNAD tissues in comparison with normal adrenal cortex. Octreotide did not exert any significant effect on cortisol secretion in a short clinical pilot study in a small number of patients with PPNAD, but long-acting SST analogs targeting multiple SSTRs may be worth investigating in this condition.
RCT Entities:
CONTEXT: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. OBJECTIVES: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease (PPNAD) tissues and to test the effect of a single injection of 100 μg of the SST analog octreotide on cortisol secretion in patients with PPNAD. SETTING AND DESIGN: The study was conducted at an academic research laboratory and clinical research center. Expression of SSTRs was examined in 26 PPNAD tissues and the immortalized PPNAD cell line CAR47. Ten subjects with PPNAD underwent a randomized, single-blind, crossover study of their cortisol secretion every 30 minutes over 12 hours (6:00 pm to 6:00 am) before and after the midnight administration of octreotide 100 μg sc. METHODS: SSTRs expression was investigated by quantitative PCR and immunohistochemistry. The CAR47 and primary cell lines were studied in vitro. The data of the 10 patients were analyzed before and after the administration of octreotide. RESULTS: All SSTRs, especially SSTR1-3, were expressed in PPNAD at significantly higher levels than in normal adrenal. SST was found to differentially regulate expression of its own receptors in the CAR47 cell line. However, the administration of octreotide to patients with PPNAD did not significantly affect cortisol secretion. CONCLUSIONS: SSTRs are overexpressed in PPNAD tissues in comparison with normal adrenal cortex. Octreotide did not exert any significant effect on cortisol secretion in a short clinical pilot study in a small number of patients with PPNAD, but long-acting SST analogs targeting multiple SSTRs may be worth investigating in this condition.
Authors: Gisbert Weckbecker; Ian Lewis; Rainer Albert; Herbert A Schmid; Daniel Hoyer; Christian Bruns Journal: Nat Rev Drug Discov Date: 2003-12 Impact factor: 84.694
Authors: L S Kirschner; J A Carney; S D Pack; S E Taymans; C Giatzakis; Y S Cho; Y S Cho-Chung; C A Stratakis Journal: Nat Genet Date: 2000-09 Impact factor: 38.330
Authors: Isabelle Bourdeau; André Lacroix; Walter Schürch; Philippe Caron; Tony Antakly; Constantine A Stratakis Journal: J Clin Endocrinol Metab Date: 2003-08 Impact factor: 5.958