Wang Z, Ren S G, Melmed S
Division of Endocrinology and Metabolism, Cedars-Sinai Research Institute, Los Angeles, California 90048-1865, USA.
Endocrinology. 1996 Jul;137(7):2947-53. doi: 10.1210/endo.137.7.8770918.
We have recently shown expression of leukemia inhibitory factor (LIF) in human fetal pituitary tissue and its in vitro induction of POMC transcription. We now use qualitative and semiquantitative RT-PCR to demonstrate that LIF and LIF-receptor (LIF-R) are constitutively expressed in the normal mouse hypothalamus and pituitary. Hypothalamic and pituitary LIF and LIF-R are significantly induced (up to 6- and 4-fold, respectively) in vivo in response to lipopolysaccharide endotoxin (LPS) administered to B6D2F1 and C57BL/6 mice. In contrast to the nearly exclusive expression of matrix-associated LIF messenger RNA (mRNA) in control hypothalamus and pituitary, both diffusible and matrix-associated LIF mRNA alternate transcripts are induced by LPS. Furthermore, the time course of peripheral ACTH-response to LPS peaks at 60 min, whereas hypothalamic LIF mRNA increase occurs at 30 min and pituitary LIF induction occurs at 60 min. These results show that mLIF is a novel LPS-inducible proinflammatory neuroendocrine cytokine and the alternatively spliced diffusible LIF may play a paracrine role in activating pituitary ACTH secretion in synergy with hypothalamic CRH, implying a mechanism for central nervous system cytokine responses to immune signals.
我们最近发现白血病抑制因子（LIF）在人胎儿垂体组织中表达，并能在体外诱导促肾上腺皮质激素原（POMC）转录。我们现在使用定性和半定量逆转录聚合酶链反应（RT-PCR）来证明LIF和LIF受体（LIF-R）在正常小鼠下丘脑和垂体中组成性表达。给B6D2F1和C57BL/6小鼠注射脂多糖内毒素（LPS）后，下丘脑和垂体中的LIF和LIF-R在体内显著诱导（分别高达6倍和4倍）。与对照下丘脑和垂体中几乎仅表达与基质相关的LIF信使核糖核酸（mRNA）相反，LPS可诱导可扩散的和与基质相关的LIF mRNA交替转录本。此外，外周促肾上腺皮质激素（ACTH）对LPS反应的时间进程在60分钟达到峰值，而下丘脑LIF mRNA在30分钟增加，垂体LIF诱导在60分钟发生。这些结果表明，小鼠LIF是一种新型的LPS诱导的促炎神经内分泌细胞因子，选择性剪接的可扩散LIF可能与下丘脑促肾上腺皮质激素释放激素（CRH）协同作用，在激活垂体ACTH分泌中发挥旁分泌作用，这意味着中枢神经系统细胞因子对免疫信号的反应机制。
