肥胖与多食伴 ACTH 缺陷：一种新的 POMC 变异体。
Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant.
机构信息
Obesity Centre CGG, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, the Netherlands.
Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, the Netherlands.
出版信息
J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3699-e3704. doi: 10.1210/clinem/dgac342.
OBJECTIVE
Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin-stimulating hormone (α-MSH) and desacetyl-α-melanocortin-stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance.
METHODS
We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant.
RESULTS
The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism.
CONCLUSION
The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control.
目的
患有前阿黑皮素原（POMC）缺陷的患者通常表现为早发性肥胖、食欲过盛、色素减退和促肾上腺皮质激素（ACTH）缺乏。啮齿动物模型表明，前激素转化酶 2 在 KKRR 区域对 ACTH 进行充分切割以产生α-黑素细胞刺激激素（α-MSH）和去乙酰-α-黑素细胞刺激激素（d-α-MSH）对于调节食物摄入和能量平衡是必需的。
方法
我们介绍了 2 位患有新型 POMC 基因突变的姐妹，该突变导致前激素转化酶 2 切割位点的 ACTH 缺陷，并对该变体进行了功能研究。
结果
患者表现为肥胖、食欲过盛和皮质醇不足，ACTH 水平明显升高，但色素沉着不受影响。他们的 ACTH 刺激黑素皮质素（MC）2 受体的效力降低，解释了他们的皮质醇不足。
结论
食欲过盛和肥胖支持这样一种证据，即 ACTH 充分切割为 α-MSH 和 d-α-MSH 对于人类的摄食控制也是必需的。
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