Human Corticotropin-Releasing Hormone Receptor: Differences in Subtype Expression between Pregnant and Nonpregnant Myometria1

There is increasing evidence that CRH, which is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, is also involved in the mechanism of human labor. The human myometrium has been shown to express several high affinity CRH receptors, although the identities of the CRH receptor subtypes have yet to be identified. To investigate further the expression of the CRH receptor in human myometrium, we used RT-PCR, fluorescent in situ hybridization and immunofluorescence to identify and localize the four subtypes, 1 alpha, 1 beta, 2 alpha, and the variant C, of the CRH receptor. Interestingly, the CRH receptor subtypes in myometrium exhibit differential expression patterns; in human pregnant myometrium at term all four receptor-subtypes were expressed, whereas only the 1 alpha- and 1 beta-receptor subtypes were found in the nonpregnant myometrium. This would suggest that CRH, acting via different receptor subtypes, is able to exert different actions on the myometrium in the pregnant state compared to the nonpregnant state. Furthermore, in the pregnant human uterus, CRH receptors were localized in both smooth muscle and fibroblasts. These findings suggest that CRH receptor expression plays an important modulatory role in myometrial and possibly in cervical function.