Stanley S A, Small C J, Murphy K G, Rayes E, Abbott C R, Seal L J, Morgan D G, Sunter D, Dakin C L, Kim M S, Hunter R, Kuhar M, Ghatei M A, Bloom S R
Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Brain Res. 2001 Mar 2;893(1-2):186-94. doi: 10.1016/s0006-8993(00)03312-6.
Cocaine- and amphetamine-regulated transcript (CART) and CART peptide are abundant in hypothalamic nuclei controlling anterior pituitary function. Intracerebroventricular (ICV) injection of CART peptide results in neuronal activation in the paraventricular nucleus (PVN), rich in corticotrophin-releasing factor (CRH) and thyrotrophin-releasing factor (TRH) immunoreactive neurons. The aims of this study were three-fold. Firstly, to examine the effects of CART peptide on hypothalamic releasing factors in vitro, secondly, to examine the effect of ICV injection of CART peptide on plasma pituitary hormones and finally to examine the effect of PVN injection of CART peptide on food intake and circulating pituitary hormones. CART(55-102) (100 nM) peptide significantly stimulated the release of CRH, TRH and neuropeptide Y from hypothalamic explants but significantly reduced alpha melanocyte stimulating hormone release in vitro. Following ICV injection of 0.2 nmol CART(55-102), a dose which significantly reduces food intake, plasma prolactin (PRL), growth hormone (GH) and adrenocorticotrophin hormone (ACTH) and corticosterone increased significantly. Following PVN injection of CART(55-102), food intake was significantly reduced only at 0.2 and 0.6 nmol. However, PVN injection of 0.02 nmol CART(55-102) produced a significant increase in plasma ACTH. ICV injection of CART peptide significantly reduces food intake. Unlike many anorexigenic peptides, there is no increased sensitivity to PVN injection of CART(55-102). In contrast, both ICV and PVN injection of CART(55-102) significantly increased plasma ACTH and release of hypothalamic CRH is significantly increased by CART peptide in vitro. This suggests that CART peptide may play a role in the control of pituitary function and in particular the hypothalamo-pituitary adrenal axis.
可卡因和苯丙胺调节转录物（CART）及CART肽在下丘脑核中含量丰富，这些核团控制着垂体前叶的功能。脑室内（ICV）注射CART肽会导致室旁核（PVN）中的神经元激活，该核富含促肾上腺皮质激素释放因子（CRH）和促甲状腺激素释放因子（TRH）免疫反应性神经元。本研究的目的有三个。第一，在体外检测CART肽对下丘脑释放因子的影响；第二，检测ICV注射CART肽对血浆垂体激素的影响；最后，检测PVN注射CART肽对食物摄入量和循环垂体激素的影响。CART(55 - 102)（100 nM）肽显著刺激下丘脑外植体释放CRH、TRH和神经肽Y，但在体外显著降低α-黑素细胞刺激素的释放。ICV注射0.2 nmol CART(55 - 102)后，该剂量能显著减少食物摄入量，血浆催乳素（PRL）、生长激素（GH）和促肾上腺皮质激素（ACTH）以及皮质酮显著增加。PVN注射CART(55 - 102)后，仅在0.2和0.6 nmol时食物摄入量显著减少。然而，PVN注射0.02 nmol CART(55 - 102)会使血浆ACTH显著增加。ICV注射CART肽显著减少食物摄入量。与许多厌食肽不同，对PVN注射CART(55 - 102)没有增加的敏感性。相反，ICV和PVN注射CART(55 - 102)均显著增加血浆ACTH，且CART肽在体外显著增加下丘脑CRH的释放。这表明CART肽可能在垂体功能的控制中发挥作用，特别是在下丘脑 - 垂体 - 肾上腺轴中。
