Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, University Children's Hospital Bern, Switzerland.
Mol Cell Endocrinol. 2010 Jan 15;314(1):101-9. doi: 10.1016/j.mce.2009.08.010. Epub 2009 Aug 20.
Neuropeptide Y (NPY) is abundantly expressed in the nervous system and acts on target cells through NPY receptors. The human adrenal cortex and adrenal tumors express NPY receptor subtype Y1, but its function is unknown. We studied Y1-mediated signaling, steroidogenesis and cell proliferation in human adrenal NCI-H295R cells. Radioactive ligand binding studies showed that H295R cells express Y1 receptor specifically. NPY treatment of H295R cells stimulated the MEK/ERK1/2 pathway, confirming that H295R cells express functional Y1 receptors. Studies of the effect of NPY and related peptide PYY on adrenal steroidogenesis revealed a decrease in 11-deoxycortisol production. RIA measurements of cortisol from cell culture medium confirmed this finding. Co-treatment with the Y1 antagonist BIBP2336 reversed the inhibitory effect of NPY on cortisol production proving specificity of this effect. At mRNA level, NPY decreased HSD3B2 and CYP21A2 expression. However NPY revealed no effect on cell proliferation. Our data show that NPY can directly regulate human adrenal cortisol production.
神经肽 Y（NPY）在神经系统中大量表达，并通过 NPY 受体作用于靶细胞。人类肾上腺皮质和肾上腺肿瘤表达 NPY 受体亚型 Y1，但功能未知。我们研究了人肾上腺 NCI-H295R 细胞中 Y1 介导的信号转导、类固醇生成和细胞增殖。放射性配体结合研究表明，H295R 细胞特异性表达 Y1 受体。NPY 处理 H295R 细胞刺激 MEK/ERK1/2 通路，证实 H295R 细胞表达功能性 Y1 受体。研究 NPY 和相关肽 PYY 对肾上腺类固醇生成的影响表明，11-脱氧皮质醇的产生减少。细胞培养物中皮质醇的 RIA 测量证实了这一发现。用 Y1 拮抗剂 BIBP2336 共同处理可逆转 NPY 对皮质醇产生的抑制作用，证明了这种作用的特异性。在 mRNA 水平上，NPY 降低了 HSD3B2 和 CYP21A2 的表达。然而，NPY 对细胞增殖没有影响。我们的数据表明，NPY 可以直接调节人肾上腺皮质醇的产生。
