Inoue T, Inui A, Okita M, Sakatani N, Oya M, Morioka H, Mizuno N, Oimomi M, Baba S
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Nihon Naibunpi Gakkai Zasshi. 1990 Jun 20;66(6):607-18. doi: 10.1507/endocrine1927.66.6_607.
There is increasing evidence that neuropeptide Y (NPY) affects the release of pituitary hormones, including adrenocorticotropic hormone (ACTH). The present study was designed to clarify the mechanism by which NPY activates the hypothalamic-pituitary-adrenal (HPA) axis in the dog. Mongrel dogs were equipped with a chronic cannula allowing intra-third (i.t.v.) or intra-lateral (i.l.v.) cerebroventricular administration. A 1.19 nmol, i.t.v. dose of NPY produced as great an ACTH and cortisol response as did equimolar ovine corticotropin releasing factor (CRF). This action of NPY was dose-dependent and shared by peptide YY (PYY) and pancreatic polypeptide (PP), other members of the PP family peptide. Intravenously (i.v.) administered NPY (1.19-11.9 nmol) was much less potent than i.v. CRF in stimulating ACTH and cortisol secretion. However, i.v. NPY significantly increased plasma ACTH and cortisol concentrations, raising the possibility that NPY may modulate the activity of corticotrophs. We next investigated the possible relationship between NPY and CRF on the HPA axis. Pretreatment with a novel CRF antagonist, alpha-helical CRF9-41 (130.9 nmol i.t.v. or 261.5 nmol i.v.), partly but significantly attenuated the ACTH and cortisol responses to i.t.v. NPY (1.19 nmol). Furthermore, adding a subthreshold dose of i.t.v. NPY (0.119 nmol) to i.t.v. CRF (1.19 nmol) or i.v. NPY (2.38 nmol) to i.v. CRF (0.595 nmol) resulted in the potentiation of CRF-induced ACTH secretion. These results indicate that NPY may activate the HPA axis in concert with CRF probably at hypothalamic and/or pituitary levels. The present findings that NPY evokes ACTH secretion and potentiates the effectiveness of CRF as a secretagogue, together with high concentrations of NPY in the hypothalamus and pituitary portal blood, suggest the NPY is involved in the multihormonal control of ACTH release.
越来越多的证据表明，神经肽Y（NPY）会影响垂体激素的释放，包括促肾上腺皮质激素（ACTH）。本研究旨在阐明NPY激活犬下丘脑-垂体-肾上腺（HPA）轴的机制。杂种犬被植入一根慢性套管，允许进行第三脑室（i.t.v.）或侧脑室（i.l.v.）内给药。1.19 nmol的i.t.v.剂量NPY产生的ACTH和皮质醇反应与等摩尔的羊促肾上腺皮质激素释放因子（CRF）相当。NPY的这一作用具有剂量依赖性，并且肽YY（PYY）和胰多肽（PP）（PP家族肽的其他成员）也具有同样的作用。静脉内（i.v.）给予的NPY（1.19 - 11.9 nmol）在刺激ACTH和皮质醇分泌方面比静脉内给予的CRF效力低得多。然而，静脉内给予NPY可显著提高血浆ACTH和皮质醇浓度，这增加了NPY可能调节促肾上腺皮质激素细胞活性的可能性。接下来，我们研究了NPY与CRF在HPA轴上可能的关系。用一种新型CRF拮抗剂α-螺旋CRF9 - 41（130.9 nmol i.t.v.或261.5 nmol i.v.）预处理，部分但显著减弱了对i.t.v. NPY（1.19 nmol）的ACTH和皮质醇反应。此外，向i.t.v. CRF（1.19 nmol）中添加亚阈值剂量的i.t.v. NPY（0.119 nmol）或向i.v. CRF（0.595 nmol）中添加i.v. NPY（2.38 nmol）会导致CRF诱导的ACTH分泌增强。这些结果表明，NPY可能与CRF协同作用，可能在下丘脑和/或垂体水平激活HPA轴。目前的研究结果表明，NPY可诱发ACTH分泌并增强CRF作为促分泌剂的效力，再加上下丘脑和垂体门脉血中高浓度的NPY，提示NPY参与了ACTH释放的多激素调控。
