The emerging role of peripheral corticotropin-releasing hormone (CRH)

Corticotropin-releasing hormone (CRH) is distributed in the brain and spinal cord and it has also been found in the myometrium, the endometrium, the placenta and diverse inflammatory sites. Traditionally, hypothalamic CRH has been considered to act indirectly in an anti-inflammatory fashion, since the end product of the hypothalamic-pituitary-adrenal axis is cortisol, a well-known anti-inflammatory compound. However, CRH produced at peripheral inflammatory sites may participate in an auto-/paracrine stimulation of inflammation. CRH in inflammatory sites seems to be involved in the activation of the Fas/Fas ligand system. Furthermore, locally produced embryonic and endometrial CRH plays a role in both the aseptic inflammatory process of implantation and the anti-rejection process that protects the fetus from the maternal immune system. There are two types of G protein-coupled CRH receptors, type 1 and 2. Pyrrolopyrimidine compounds, such as antalarmin, have been developed as CRH receptor antagonists. The systemic administration of antalarmin blocks pituitary CRH receptors and the CRH-induced secretion of adrenocorticotropin. Additonally, antalarmin has been shown to reduce the inflammatory-like reaction of the endometrium to the invading blastocyst, with a possible therapeutic potential as a non-steroidal inhibitor of pregnancy at its early stages.