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.
J Clin Endocrinol Metab. 2014 May;99(5):E891-901. doi: 10.1210/jc.2013-2657. Epub 2014 Feb 10.
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.
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.
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.
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.
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.
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.
生长抑素(SST)受体(SSTRs)在许多组织中表达,包括肾上腺皮质,但它们在皮质醇分泌中的作用尚未得到很好的描述。
本研究旨在研究 SSTRs 在肾上腺皮质和原发性色素性结节性肾上腺皮质疾病(PPNAD)组织培养的肾上腺皮质细胞中的表达,并检测单次注射 100μg SST 类似物奥曲肽对 PPNAD 患者皮质醇分泌的影响。
该研究在学术研究实验室和临床研究中心进行。检查了 26 例 PPNAD 组织和永生化 PPNAD 细胞系 CAR47 中 SSTRs 的表达。10 例 PPNAD 患者接受了一项随机、单盲、交叉研究,在奥曲肽 100μg sc 午夜给药前后,每 30 分钟测量 12 小时(下午 6:00 至早上 6:00)的皮质醇分泌。
通过定量 PCR 和免疫组织化学检测 SSTRs 的表达。研究了 CAR47 和原代细胞系的体外表达。对 10 例患者的奥曲肽给药前后的数据进行了分析。
与正常肾上腺相比,所有 SSTRs,特别是 SSTR1-3,在 PPNAD 中表达水平显著升高。SST 被发现可调节 CAR47 细胞系中自身受体的表达。然而,奥曲肽给药对 PPNAD 患者的皮质醇分泌没有显著影响。
与正常肾上腺皮质相比,PPNAD 组织中 SSTRs 过度表达。在少数 PPNAD 患者的短期临床初步研究中,奥曲肽对皮质醇分泌没有产生任何显著影响,但针对多种 SSTR 的长效 SST 类似物在这种情况下可能值得研究。