LEUKEMIA INHIBITORY FACTOR (LIF) INDUCES ACUTE ADRENOCORTICOTROPIC HORMONE (ACTH) SECRETION IN FETAL RHESUS MACAQUE PRIMATES - A NOVEL DYNAMIC TEST OF PITUITARY-FUNCTION

Leukemia Inhibitory Factor (LIF), a pituitary cytokine, and LIF recept ors are expressed in human fetal and adult adenohypophyseal cells. LIF induces adrenocorticotropin hormone (ACTH) secretion in vitro and pot ently synergizes with both corticotropin-releasing hormone (CRH) and c AMP-induced proopiomelanocortin (POMC) transcription. We therefore inv estigated the effects of intra-carotid administration of recombinant h uman LIF to chronically catheterized fetal non-human primates. LIF ind uced fetal monkey ACTH secretion in a time- and dose dependent manner. Maximal ACTH induction (12-fold) was achieved with 100 mu g/kg after 60 minutes (p<0.01). CRH (10 mu g/kg) also induced ACTH secretion 4.8- fold at 60 minutes. Co-injection of LIF (50 mu g/kg) and CRH (10 mu g/ kg) synergistically induced ACTH levels in a time-dependent manner up to 23-fold after 60 minutes. Thus, LIF alone induces ACTH secretion an d LIF acts in synergy with CRH in vivo. As LIF is expressed early in h uman fetal pituitary development, and potentiates corticotroph functio n both in vitro and in vivo, this immune-regulatory cytokine may be us eful for clinical testing of the hypothalamic-pituitary-adrenal axis.