肽能G蛋白偶联受体对肾上腺功能的调节:从实验台到床边和背部。

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2022-11-25 DOI:10.1210/endrev/bnac011
Livia Lenzini, Brasilina Caroccia, Teresa Maria Seccia, Gian Paolo Rossi
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引用次数: 1

摘要

肾上腺皮质激素和肾上腺髓质激素分泌的改变在原发性醛固酮增多症(PA)、库欣和嗜铬细胞瘤的临床综合征中起作用。此外,肾上腺皮质激素产生的改变和/或肾上腺髓质因子的异常释放与其他几种疾病有关,包括高血压、充血性心力衰竭、肝硬化、肾病综合征、原发性肾性肾病、肾血管性高血压、Addison病、Bartter、Gitelman和男性化综合征。因此,了解肾上腺功能的调节以及肾上腺皮质和髓质之间的相互作用是了解这些疾病机制的先决条件。越来越多的证据表明,肾上腺激素生物合成的调节是一个比原先认为的复杂得多的过程,因为它涉及到几个因素,每个因素相互合作。此外,肾上腺皮质和髓质之间紧密的血管和神经连接是生理上相关的自分泌/旁分泌相互作用的基础,涉及多种肽。除了在常见的肾上腺疾病中发挥病理生理作用外,这些复杂的机制也可能干预罕见疾病,如嗜铬细胞瘤合并肾上腺库欣或PA,以及PA与库欣共存,其机制在分子水平上仍有待充分了解。肽信号诱导的G蛋白偶联受体(gpcr)异二聚化是一种新的调节肾上腺激素合成和释放的新机制。在这篇综述中,我们将研究目前关于肽通过gpcr在肾上腺激素分泌调节中的作用的知识,特别关注自分泌-旁分泌信号。
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Peptidergic G Protein-Coupled Receptor Regulation of Adrenal Function: Bench to Bedside and Back.

An altered secretion of adrenocortical and adrenomedullary hormones plays a role in the clinical syndromes of primary aldosteronism (PA), Cushing, and pheochromocytoma. Moreover, an altered production of adrenocortical hormones and/or an abnormal release of factors by the adrenal medulla are involved in several other diseases, including high blood pressure, congestive heart failure, liver cirrhosis, nephrotic syndrome, primary reninism, renovascular hypertension, Addison disease, Bartter, Gitelman, and virilization syndromes. Understanding the regulation of adrenal function and the interactions between adrenal cortex and medulla is, therefore, the prerequisite for mechanistic understanding of these disorders. Accumulating evidence indicates that the modulation of adrenal hormone biosynthesis is a process far more complex than originally thought, as it involves several factors, each cooperating with the other. Moreover, the tight vascular and neural interconnections between the adrenal cortex and medulla underlie physiologically relevant autocrine/paracrine interactions involving several peptides. Besides playing a pathophysiological role in common adrenal diseases, these complex mechanisms could intervene also in rare diseases, such as pheochromocytoma concomitant with adrenal Cushing or with PA, and PA co-occurring with Cushing, through mechanisms that remain to be fully understood at the molecular levels. Heterodimerization of G protein-coupled receptors (GPCRs) induced by peptide signaling is a further emerging new modulatory mechanism capable of finely tuning adrenal hormones synthesis and release. In this review we will examine current knowledge on the role of peptides that act via GPCRs in the regulation of adrenal hormone secretion with a particular focus on autocrine-paracrine signals.

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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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