Disrupted murine leukemia inhibitory factor (LIF) gene attenuates adrenocorticotropic hormone (ACTH) secretion.
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.
Akita
S
S
Department of Medicine, Cedars-Sinai Research Institute- UCLA School of Medicine, Los Angeles, CA 90048, USA.
Malkin
J
J
Melmed
S
S
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D006579:Heterozygote; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins / Q000096:biosynthesis; D011995:Recombination, Genetic
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone