Department of Endocrinology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Endocrinol. 2010 Aug;163(2):293-9. doi: 10.1530/EJE-10-0058. Epub 2010 May 11.
Aberrant adrenal expression of various hormone receptors has been identified in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing cortisol hypersecretion regulated by hormones other than ACTH. We aimed to determine aberrant expression of multiple hormone receptors in vivo and in vitro in adrenal tissue of a patient with AIMAH.
The design of the study includes clinical case description, and biochemical and immunohistochemical analysis to demonstrate aberrant expression of multiple hormone receptors in AIMAH.
The subject of the study is a male diagnosed with Cushing's syndrome because of AIMAH. Directly after laparoscopic removal of the adrenals, adrenal tissue was incubated with and without test substances (ACTH, forskolin, arginine vasopressin (AVP), desmopressin, epinephrine, norepinephrine, purified human chorionic gonadotropin (hCG), metoclopramide and the combinations of AVP with ACTH, epinephrine and metoclopramide). LH/hCG-receptor (hCG-R) immunohistochemistry and RT-PCR analyses were performed to demonstrate aberrant expression of LH/hCG-R and V(1-3)-AVPR.
AIMAH was characterized by in vivo cortisol responsiveness to AVP and in vitro cortisol responses to AVP, hCG, epinephrine, and norepinephrine suggesting aberrant adrenal expression of the receptors for AVP (the V(1-3)-AVPRs), catecholamines (the beta-AR), and LH (the LH/hCG-R). Incubation with combinations of AVP and ACTH and of AVP with epinephrine induced a stronger cortisol response compared with incubation with the individual agents. Moreover, we demonstrated adrenal V(1-3)-AVPR and LH/hCG-R expression.
AIMAH tissue may simultaneously express multiple aberrant hormone receptors, and individual ligands may potentiate each other regarding cell proliferation and cortisol production.
在 ACTH 非依赖性大结节性肾上腺增生（AIMAH）中，各种激素受体的肾上腺表达异常已经确定，导致受 ACTH 以外的激素调节的皮质醇分泌过多。我们旨在确定 AIMAH 肾上腺组织中体内和体外多种激素受体的异常表达。
本研究的设计包括临床病例描述以及生化和免疫组织化学分析，以证明 AIMAH 中多种激素受体的异常表达。
研究对象为一名男性，因 AIMAH 被诊断为库欣综合征。在腹腔镜切除肾上腺后，直接用和不用测试物质（ACTH、福司可林、精氨酸加压素（AVP）、去氨加压素、肾上腺素、去甲肾上腺素、纯化人绒毛膜促性腺激素（hCG）、甲氧氯普胺以及 AVP 与 ACTH、肾上腺素和甲氧氯普胺的组合）孵育肾上腺组织。进行 LH/hCG 受体（hCG-R）免疫组织化学和 RT-PCR 分析，以证明 LH/hCG-R 和 V（1-3）-AVPR 的异常表达。
AIMAH 的特征是体内对 AVP 的皮质醇反应性和体外对 AVP、hCG、肾上腺素和去甲肾上腺素的皮质醇反应性，提示肾上腺表达异常的受体包括 AVP（V（1-3）-AVPRs）、儿茶酚胺（β-AR）和 LH（LH/hCG-R）。与单独使用这些药物相比，与 AVP 和 ACTH 联合孵育以及与 AVP 和肾上腺素联合孵育诱导更强的皮质醇反应。此外，我们还证明了肾上腺 V（1-3）-AVPR 和 LH/hCG-R 的表达。
AIMAH 组织可能同时表达多种异常激素受体，并且单个配体可能在细胞增殖和皮质醇产生方面相互增强。
