Leukemia inhibitory factor as an intrapituitary regulator of pro-opiomelanocortin gene expression and corticotrope ontogeny

Along with the well characterized control of pituitary function by hypothalamic hormones, several cytokines mediate signaling between the neuroendocrine and immune systems. Interleukin-1 (IL-1), IL-6, tumor necrosis factor-a and, recently, leukemia inhibitory factor (LIF) and IL-11 (1, 2) are the most thoroughly characterized. LIF belongs to the IL-6 cytokine family, together with IL-6, IL-11, oncostatin M, cilary neuro- tropic factor and cardiotropin-1. LIF was originally characterized and so named for its ability to promote the differentiation of a mouse myeloid leukemic cell line (3). LIF is a pleiotropic cytokine and has diverse biological activities, including regulation of hematopoietic cell proliferation and differentiation, stimulation of neuronal growth and development, bone formation, and prepara- tion of the uterus for embryo implantation. Melmed and his colleagues have shown that LIF participates in regulating gene expression of pro-opiomelanocortin (POMC), in addition to corticotropin-releasing hormone (CRH) and glucocorticoids (4-6).