Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Room G2-118, 1105 AZ Amsterdam, The Netherlands.
Eur J Endocrinol. 2013 Feb 15;168(3):361-9. doi: 10.1530/EJE-12-0750. Print 2013 Mar.
The melanocortin 4 receptor (MC4R) is an essential regulator of energy homeostasis and metabolism, and MC4R mutations represent the most prevalent monogenetic cause of obesity in humans known to date. Hypothalamic MC4Rs in rodents are well characterized in neuroanatomical and functional terms, but their expression pattern in the human hypothalamus is unknown.
To determine the topographic distribution and identity of cells expressing MC4R mRNA in the human hypothalamus, locked nucleic acid in situ hybridization was performed on nine human postmortem hypothalami. In addition, co-expression of MC4R with glial fibrillary acidic protein (GFAP), vasopressin/oxytocin (AVP/OXT), corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), agouti-related protein (AgRP), and α-melanocyte stimulating hormone (α-MSH) was examined.
Most intense MC4R mRNA expression was present in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and the nucleus basalis of Meynert. Most MC4R-positive cells in the SON also expressed AVP/OXT. Co-expression with AVP/OXT in the PVN was less abundant. We did not observe co-expression of MC4R mRNA and GFAP, CRH, NPY, AgRP, or α-MSH. However, fiber-like staining of NPY, AgRP, and α-MSH was found adjacent to MC4R-positive cells in the PVN.
Expression of MC4R mRNA in the human hypothalamus is widespread and in close approximation to endogenous MC4R binding partners AgRP and α-MSH.
黑皮质素 4 受体（MC4R）是能量平衡和代谢的重要调节剂，MC4R 突变是迄今为止已知的人类肥胖最常见的单基因病因。啮齿动物的下丘脑 MC4R 在神经解剖学和功能方面得到了很好的描述，但它们在人类下丘脑中的表达模式尚不清楚。
为了确定人类下丘脑 MC4R mRNA 表达的拓扑分布和细胞特征，我们对 9 个人体死后下丘脑进行了锁核酸原位杂交。此外，还检查了 MC4R 与胶质纤维酸性蛋白（GFAP）、血管加压素/催产素（AVP/OXT）、促肾上腺皮质激素释放激素（CRH）、神经肽 Y（NPY）、刺鼠相关蛋白（AgRP）和α-促黑素细胞激素（α-MSH）的共表达。
最强的 MC4R mRNA 表达存在于室旁核（PVN）、视上核（SON）和梅尼埃基底核。SON 中大多数 MC4R 阳性细胞也表达 AVP/OXT。在 PVN 中，与 AVP/OXT 的共表达较少。我们没有观察到 MC4R mRNA 与 GFAP、CRH、NPY、AgRP 或α-MSH 的共表达。然而，在 PVN 中，我们发现 NPY、AgRP 和α-MSH 的纤维样染色与 MC4R 阳性细胞相邻。
MC4R mRNA 在人类下丘脑中的表达广泛，与内源性 MC4R 结合伴侣 AgRP 和α-MSH 接近。
