Corticotropin-releasing hormone stimulates angiogenesis and epithelial tumor growth in the skin

The hypothalamic neuropeptide corticotropin-releasing hormone is the major hypothalamic regulator of the endocrine pituitary-adrenal axis. Corticotrop in-releasing hormone is also expressed in many peripheral sites, where its functions are unclear. It is also secreted by diverse neoplasms, where it m ay be associated with malignant behavior. To provide information regarding the function of corticotropin-releasing hormone in peripheral sites and in tumors, we asked whether corticotropin-releasing hormone has angiogenic pro perties, In vitro, we found that human corticotropin-releasing hormone spec ifically stimulates endothelial chemotaxis via a corticotropin-releasing ho rmone receptor-dependent mechanism. In vivo, subcutaneous inoculation of nu de mice with human epithelial tumor cells engineered to secrete corticotrop in-releasing hormone was associated with significantly enhanced angiogenesi s (2.3-fold over control) and tumor growth (5-fold over control). Periphera l corticotropin-releasing hormone may thus enhance local angiogenesis, whic h may provide clues to its function outside of the nervous system.