Akita S, Malkin J, Melmed S
Department of Medicine, Cedars-Sinai Research Institute- UCLA School of Medicine, Los Angeles, CA 90048, USA.
Endocrinology. 1996 Jul;137(7):3140-3. doi: 10.1210/endo.137.7.8770940.
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.
白血病抑制因子（LIF）及其在人和小鼠垂体细胞中的受体在促肾上腺皮质激素细胞和生长激素细胞中大量表达。由于LIF诱导阿黑皮素原（POMC）转录，且脂多糖（LPS）介导的应激也诱导下丘脑和垂体LIF表达，我们研究了LIF基因敲除（LIF KO）小鼠的促肾上腺皮质激素（ACTH）分泌情况。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水平更低（为野生型同窝小鼠的38%，p=0.014）。通过植入皮下渗透泵给予LIF（1.2微克/天）可在三天内恢复ACTH（与用磷酸盐缓冲液（PBS）替代相比，p=0.006）和皮质酮（与用PBS替代相比，p=0.02）水平。五天后，取出泵，两天后，ACTH水平恢复到治疗前的值。相比之下，LIF替代LIF KO小鼠会使生长激素（GH）浓度降低。因此，LIF KO小鼠中LIF的缺失导致ACTH水平降低，表明LIF在垂体中对下丘脑-垂体-肾上腺（HPA）轴的发育和调节起着重要作用。
