Jones P M, Ghatei M A, Steel J, O'Halloran D, Gon G, Legon S, Burrin J M, Leonhardt U, Polak J M, Bloom S R
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Endocrinology. 1989 Jul;125(1):334-41. doi: 10.1210/endo-125-1-334.
Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.
神经肽Y（NPY）是胰多肽家族的一个由36个氨基酸组成的成员，通过放射免疫分析和免疫细胞化学方法发现其存在于大鼠垂体前叶中。通过Northern印迹分析在垂体中鉴定出了NPY前体激素信使核糖核酸（mRNA）。通过确定甲状腺激素调控对肽合成的影响来研究NPY可能的调节机制。为作比较，还研究了另外三种垂体前叶神经肽，即神经降压素（NT）、P物质（SP）和血管活性肠肽（VIP）。发现甲状腺功能减退会显著增加垂体中NPY、SP和VIP的含量及其各自的mRNA，但会减少NT的量。免疫细胞化学显示，对照大鼠垂体前叶中散在细胞内的NPY免疫反应性非常弱，但在甲状腺功能减退的大鼠中可见更多阳性细胞，且染色相对较强。这些阳性细胞被鉴定为促甲状腺激素细胞的一个亚群。在T4诱导的甲状腺功能亢进中，NPY、NT和VIP水平未受影响，而SP浓度大幅下降。促甲状腺激素释放激素（TRH）处理使NT减少，对NPY、SP或VIP无影响。这些变化仅在垂体中出现；下丘脑肽和mRNA水平未发生净变化。由于垂体肽和mRNA水平的变化是协同发生的，似乎甲状腺激素状态的调节至少部分直接发生在基因转录水平。甲状腺功能减退时这4种调节肽的变化及其对垂体功能已知的强大作用表明，它们在控制垂体分泌改变方面可能具有显著的旁分泌或自分泌影响。
