Corticotropin releasing hormone (CRH) in normal and pregnant uterus: physiological implications

Corticotropin-releasing hormone, is a hypothalamic neuropeptide, responsible not only for the endocrine but also the autonomic, immunological and behavioural responses of mammalian organisms to stress. CRH is also expressed in female reproductive tissues, such as placenta and uterus. Multiple sites within the pregnant uterine cavity express the CRH gene, including the trophoblasts, fetal membranes (chorion, amnion) and decidua. The trophoblastic syncytium appears to be the major source of placental CRH. It is postulated that placental CRH influences the HPA axis of either mother or fetus and participates at the initiation of labour. Recent findings show that human and rat uterus express the CRH gene. Epithelial cells of both species are the main source of endometrial CRH, while stroma does not seem to express it, unless it differentiates to decidua. Estrogens and glucocorticoids inhibit and prostaglandin E2 stimulates the promoter of human CRH gene in transfected human endometrial cells, suggesting that endometrial CRH gene expression is under the control of these agents. Moreover, in rats, endometrial CRH expression is significantly higher at the implantation sites, compared to that at the inter-implantation uterine regions. Given the proinflammatory/vasoregulatory properties of CRH, we hypothesize that endometrial CRH may participate in the regulation of intrauterine phenomena, such as blastocyst implantation, endometrial vascularization and myometrial contractility.