Leukemia inhibitory factor (LIF) induces acute adrenocorticotrophic hormone (ACTH) secretion in fetal rhesus macaque primates: a novel dynamic test of pituitary function.
Leukemia Inhibitory Factor (LIF), a pituitary cytokine, and LIF receptors are expressed in human fetal and adult adenohypophyseal cells. LIF induces adrenocorticotropin hormone (ACTH) secretion in vitro and potently synergizes with both corticotropin-releasing hormone (CRH) and cAMP-induced pro-opiomelanocortin (POMC) transcription. We therefore investigated the effects of intra-carotid administration of recombinant human LIF to chronically catheterized fetal non-human primates. LIF induced fetal monkey ACTH secretion in a time- and dose dependent manner. Maximal ACTH induction (12-fold) was achieved with 100 micrograms/kg after 60 minutes (p < 0.01). CRH (10 micrograms/kg) also induced ACTH secretion 4.8-fold at 60 minutes. Co-injection of LIF (50 micrograms/kg) and CRH (10 micrograms/kg) synergistically induced ACTH levels in a time-dependent manner up to 23-fold after 60 minutes. Thus, LIF alone induces ACTH secretion and LIF acts in synergy with CRH in vivo. As LIF is expressed early in human fetal pituitary development, and potentiates corticotroph function both in vitro and in vivo, this immuno-regulatory cytokine may be useful for clinical testing of the hypothalamic-pituitary-adrenal axis.
Akita
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Department of Medicine, Cedars-Sinai Research Institute - UCLA School of Medicine 90048, USA.
Conn
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PM
Melmed
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D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002339:Carotid Arteries; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007269:Injections, Intra-Arterial; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D008253:Macaca mulatta; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D011994:Recombinant Proteins; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone