Leukemia inhibitory factor signaling is implicated in embrionic development of the HPA axis.

Leukemia inhibitory factor (LIF) is expressed in the hypothalamic-pituitary adrenal (HPA) axis and stimulates pituitary POMC transcription. The role of LIF receptor signaling in HPA axis development was examined. Lifr -/- and Lifr +/+ fetuses were obtained by Cesarean section on E18.5. Despite a 3-fold induction of hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were decreased in Lifr -/- mice. High CRH may be caused by increased central TNFalpha and IL-6 expression. Lifr -/- mice demonstrate elevated pituitary glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA and protein levels, indicating the importance of LIF signaling for HPA axis development.