Chesnokova V, Auernhammer C J, Melmed S
Division of Endocrinology and Metabolism, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles 90048, USA.
Endocrinology. 1998 May;139(5):2209-16. doi: 10.1210/endo.139.5.6016.
Recently, we have shown that human fetal pituitary, mouse corticotroph AtT20 cells, and murine hypothalamus and pituitary express leukemia inhibitory factor (LIF). LIF knockout mice (LIFKO), heterozygous and wild type (wt), of B6D2F1 genetic background were used to examine whether LIF may play a role in the regulation of the hypothalamo-pituitary-adrenal axis in vivo. Resting levels of plasma ACTH and corticosterone were similar in all three genotypes. However, LIFKO mice did not respond to 30-min restraint and 45-min immobilization stress with increased plasma ACTH. Increased circulating ACTH was only observed in LIFKO mice after very short immobilization stress (15 min), but this ACTH level was lower than in wt animals (P < 0.05). Injection of mycobacterial adjuvant resulted in a 2-fold increase of corticosterone levels 7 days after treatment in wt, but not LIFKO, mice (P < 0.05). Pituitary POMC messenger RNA (mRNA) levels were very low in LIFKO animals. Although 15 and 45 min of immobilization stress resulted in enhanced POMC mRNA content in all three groups, this elevation was lowest in LIFKO mice. Injection of 12 microg murine LIF to LIFKO and normal C57BL/6 animals resulted in increased plasma ACTH and corticosterone levels and elevated pituitary POMC mRNA levels in both LIF-repleted and LIF-depleted mice. Thus, LIF appears to play an important role in activating the hypothalamo-pituitary-adrenal axis during stress and inflammation.
最近，我们发现人类胎儿垂体、小鼠促肾上腺皮质激素分泌细胞AtT20、以及小鼠下丘脑和垂体均表达白血病抑制因子（LIF）。我们使用了具有B6D2F1遗传背景的LIF基因敲除小鼠（LIFKO）、杂合子和野生型（wt）小鼠，来研究LIF在体内是否可能参与下丘脑-垂体-肾上腺轴的调节。所有三种基因型小鼠的血浆促肾上腺皮质激素（ACTH）和皮质酮的基础水平相似。然而，LIFKO小鼠在受到30分钟束缚和45分钟固定应激后，血浆ACTH水平并未升高。仅在LIFKO小鼠受到非常短时间的固定应激（15分钟）后，才观察到循环ACTH升高，但该ACTH水平低于野生型动物（P < 0.05）。注射分枝杆菌佐剂后，野生型小鼠在治疗7天后皮质酮水平增加了2倍，但LIFKO小鼠未出现这种情况（P < 0.05）。LIFKO动物垂体前阿黑皮素原（POMC）信使核糖核酸（mRNA）水平非常低。尽管15分钟和45分钟的固定应激使所有三组小鼠的POMC mRNA含量均增加，但LIFKO小鼠的这种升高幅度最小。向LIFKO和正常C57BL/6动物注射12微克小鼠LIF后，补充LIF和未补充LIF的小鼠血浆ACTH和皮质酮水平均升高，垂体POMC mRNA水平也升高。因此，LIF似乎在应激和炎症过程中激活下丘脑-垂体-肾上腺轴方面发挥重要作用。
