Disrupted murine leukemia inhibitory factor (LIF) gene attenuates adrenocorticotropic hormone (ACTH) secretion.
Disrupted murine leukemia inhibitory factor (LIF) gene attenuates adrenocorticotropic hormone (ACTH) secretion.
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DOI：
10.1210/endo.137.7.8770940
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发表时间：
1996-07
期刊：
影响因子：
4.8
通讯作者：
S. Akita;J. Malkin;S. Melmed
中科院分区：
文献类型：
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作者：
S. Akita;J. Malkin;S. Melmed
白血病抑制因子（LIF）及其受体在人和小鼠垂体细胞中大量表达于促肾上腺皮质激素细胞和促生长激素细胞。由于LIF诱导POMC转录，LPS介导的应激也诱导下丘脑和垂体LIF表达，我们研究了LIF敲除（LIF KO）小鼠的ACTH分泌。LIF KO小鼠的基础ACTH水平较低（p<0.05），禁食36小时后，LIF KO小鼠的ACTH水平较低（WT同窝出生小鼠的38%，p=0.014）。通过植入皮下渗透泵递送LIF（1.2微克/天）在三天内恢复ACTH（p=0.006 vs PBS替代）和皮质酮（p=0.02 vs PBS替代）水平。五天后，泵被移除，两天后，ACTH水平恢复到治疗前的水平。相比之下，LIF KO小鼠通过LIF替代减弱GH浓度。因此，在LIF KO小鼠中LIF的缺乏导致ACTH水平减弱，表明LIF在HPA轴的发育和调节中起重要的垂体内作用。
Leukemia Inhibitory Factor (LIF) and its receptors in human and mouse pituicytes are expressed abundantly in corticotrophs and somatotrophs. As LIF induces POMC transcription and LPS-mediated stress also induces hypothalamic and pituitary LIF expression, we studied ACTH secretion in LIF knockout (LIF KO) mice. Basal ACTH levels were lower in LIF KO mice (p<0.05) and after 36 hours fasting, LIF KO mice had lower ACTH levels (38% of WT littermates, p=0.014 ). Delivery of LIF (1.2 microg/day) via implantation of subcutaneous osmotic pumps restored ACTH (p=0.006 vs PBS replacement) and corticosterone (p=0.02 vs PBS replacement) levels within three days. After five days, pumps were removed and two days later, ACTH levels had reverted to pre-treatment values. In contrast, GH concentrations were attenuated by LIF replacement to LIF KO mice. Thus, absence of LIF in LIF KO mice results in attenuated ACTH levels indicating that LIF plays an important intrapituitary role in HPA axis development and regulation.