LaPaglia N, Steiner J, Kirsteins L, Emanuele M, Emanuele N
Department of Medicine, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
J Endocrinol. 1998 Oct;159(1):79-83. doi: 10.1677/joe.0.1590079.
Proper nutritional status is critical for maintaining growth and metabolic function, playing an intimate role in neuroendocrine regulation. Leptin, the recently identified product of the obese gene, may very well be an integral signal which regulates neuroendocrine responses in times of food deprivation. The present study examines leptin's ability to regulate hormonal synthesis and secretion within the GRF-GH-IGF axis in the adult male rat during almost 3 days of fasting. Serum levels of GH and IGF-I were drastically suppressed by fasting. Daily leptin administration was able to fully prevent the fasting-induced fall in serum GH. Leptin failed to restore IGF-I to control levels, however, suggesting possible GH resistance. Fasting caused an insignificant increase in GH mRNA, while leptin injections significantly increased steady-state levels of this message. The GRF receptor (GRFr) message was not altered with fasting or leptin treatment. Leptin also exhibited effects at the hypothalamic level. Fasting induced a sharp fall in GRF mRNA expression and leptin injections partially prevented this fall. However, there were no observed changes in the hypothalamic GRF content. These results provide evidence that leptin may function as a neuromodulator of the GRF-GH-IGF axis communicating to this hormonal system the nutritional status of the animal.
适当的营养状况对于维持生长和代谢功能至关重要，在神经内分泌调节中发挥着密切作用。瘦素是最近发现的肥胖基因产物，很可能是一种在食物缺乏时调节神经内分泌反应的重要信号。本研究考察了在成年雄性大鼠近3天禁食期间，瘦素调节生长激素释放因子-生长激素-胰岛素样生长因子（GRF-GH-IGF）轴内激素合成和分泌的能力。禁食使血清生长激素（GH）和胰岛素样生长因子-Ⅰ（IGF-Ⅰ）水平大幅降低。每日注射瘦素能够完全防止禁食引起的血清GH下降。然而，瘦素未能使IGF-Ⅰ恢复到对照水平，提示可能存在GH抵抗。禁食使GH信使核糖核酸（mRNA）略有增加，而注射瘦素显著增加了该信使的稳态水平。生长激素释放因子受体（GRFr）信使核糖核酸不受禁食或瘦素治疗的影响。瘦素在下丘脑水平也表现出作用。禁食导致生长激素释放因子信使核糖核酸表达急剧下降，注射瘦素可部分防止这种下降。然而，下丘脑生长激素释放因子含量未见变化。这些结果证明，瘦素可能作为GRF-GH-IGF轴内的神经调节剂，将动物的营养状况传递给该激素系统。
