Sexual dimorphism in the development and function of the melanocortin system.

IF 8 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Reviews in Endocrine & Metabolic Disorders Pub Date : 2025-06-24 DOI:10.1007/s11154-025-09983-4

Marc Claret, Roberta Haddad-Tóvolli

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Abstract

The melanocortin system is fundamental for the regulation of whole-body energy homeostasis. This system consists of pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARH), as well as downstream neurons expressing melanocortin receptors (MCRs) located in various brain regions. Emerging evidence highlights significant anatomical and functional sex differences within the melanocortin system, influencing sex-dimorphic metabolic adaptations, the regulation of appetite and energy expenditure and susceptibility to metabolic conditions. These differences are primarily shaped by sex hormones, genetic and environmental factors as well as distinct neurocircuitry organization between males and females. These sex-specific regulatory mechanisms have important implications for the pathophysiology of metabolic disorders, including obesity, type 2 diabetes, and eating disorders. In this review, we explore current knowledge on sex differences in the development and function of the melanocortin system and how this is translated into sex-dimorphic control of metabolism. This emphasizes the need to incorporate sex as a critical variable in both metabolic research and clinical studies. Understanding these mechanisms may provide more precise and effective therapeutic strategies for metabolic disorders, obesity, and appetite dysregulation in both sexes.

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黑素皮质素系统发育和功能中的两性二态性。

黑素皮质素系统是调节全身能量稳态的基础。该系统包括位于下丘脑弓状核（ARH）的前阿皮质素（POMC）和阿皮质素相关肽（AgRP）神经元，以及位于脑各区域表达黑素皮质素受体（mcr）的下游神经元。新出现的证据强调了黑素皮质素系统中显著的解剖和功能性别差异，影响性别二态代谢适应、食欲和能量消耗的调节以及对代谢条件的易感性。这些差异主要是由性激素、遗传和环境因素以及男性和女性之间不同的神经回路组织形成的。这些性别特异性调节机制对代谢紊乱（包括肥胖、2型糖尿病和饮食失调）的病理生理学具有重要意义。在这篇综述中，我们探讨了目前关于黑素皮质素系统发育和功能的性别差异的知识，以及这是如何转化为代谢的性别二态控制的。这强调了在代谢研究和临床研究中将性别作为一个关键变量的必要性。了解这些机制可以为两性的代谢紊乱、肥胖和食欲失调提供更精确和有效的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reviews in Endocrine & Metabolic Disorders 医学-内分泌学与代谢

CiteScore

14.70

自引率

1.20%

发文量

审稿时长

>12 weeks

期刊介绍： Reviews in Endocrine and Metabolic Disorders is an international journal dedicated to the field of endocrinology and metabolism. It aims to provide the latest advancements in this rapidly advancing field to students, clinicians, and researchers. Unlike other journals, each quarterly issue of this review journal focuses on a specific topic and features ten to twelve articles written by world leaders in the field. These articles provide brief overviews of the latest developments, offering insights into both the basic aspects of the disease and its clinical implications. This format allows individuals in all areas of the field, including students, academic clinicians, and practicing clinicians, to understand the disease process and apply their knowledge to their specific areas of interest. The journal also includes selected readings and other essential references to encourage further in-depth exploration of specific topics.