High expression of neuropeptide Y receptors in tumors of the human adrenal gland and extra-adrenal paraganglia

Purpose: Recently, a role of neuropeptide Y (NPY) in tumor biology was suggested based on the high density of NPY receptors in breast and ovarian cancers. The high frequency of NPY receptors in steroid hormone-producing ovarian sex cord-stromal tumors, together with the known influence of NPY on steroid hormone and catecholamine secretion in the rodent adrenal gland, led to the investigation of NPY receptor expression in the human adrenal gland and related tumors. Experimental Design: Fifteen adrenal cortical tumors, 20 paragangliomas, 23 pheochromocytomas, 20 neuroblastomas, and 8 normal adrenal glands were investigated by in vitro NPY receptor autoradiography using I-125-labeled peptide YY in competition experiments with receptor subtype selective analogs. Results: Ninety three percent of cortical tumors express Y1, 35% of pheochromocytomas and 61% of paragangliomas express Y1 and Y2, and 90% of neuroblastomas express Y2 receptors. The NPY receptors in pheochromocytomas, paragangliomas, and neuroblastomas are often expressed concomitantly with the NPY hormone detected immunohistochemically. The adrenal cortex strongly expresses Y1, whereas no NPY receptors are found in the adrenal medulla. Conclusions: These receptor data suggest a role of NPY in adrenal cortical tumors and, together with the strong NPY innervation of the cortex, a physiologic role in the adrenal gland, mediated by Y1 receptors. These NPY receptors are a potential new molecular target for the therapy of malignant tumors.