Maternal plasma corticotropin-Releasing Hormone (CRH) rises from midgestation to term and increases further during labor in pregnant women. The primate placenta contains both the CRH peptide and its gene and is the likely source of circulating CRH. In the present study, we examined CRH messenger RNA (mRNA) and peptide expression in fetal membranes and the placenta of 14 pregnant rhesus monkeys (140-161 days gestational age) using Northern blot analysis, in situ hybridization, and immunocytochemistry to define the cellular distribution of CRH during the last third of pregnancy and in relation to onset of both spontaneous term and androstenedione-induced preterm labor. To localize the target tissues for placental CRH, CRH receptor gene expression was also studied in the fetal membranes and placenta. CRH mRNA in the placenta was of similar molecular size to hypothalamic CRH. Placental CRH mRNA increased significantly during both spontaneous term and androstenedione-induced preterm labor (P < 0.05). Placental CRH peptide detected by CRH immunostaining also increased, matching the changes of CRH mRNA. In situ hybridization and immunocytochemistry demonstrated that syncytiotrophoblast cells are the major cell type expressing CRH mRNA and producing CRH protein. CRH mRNA was not detected in either amnion or chorion. CRH receptor complementary DNA and oligo probes that successfully hybridized CRH receptor mRNA in the fetal rhesus monkey hypothalamus failed to reveal the existence of CRH receptor mRNA in amnion, chorion, and placenta by Northern blot hybridization. In conclusion, placental but not fetal membrane syncytiotrophoblasts are the source of CRH production in the pregnant rhesus monkey. The significant increase in CRH peptide and mRNA content in both spontaneous term and androstenedione-induced preterm labor indicates a role for CRH in the process of parturition. The lack of CRH receptor mRNA in either the fetal membranes or the placenta suggests that placental CRH exerts its action at sites other than these tissues.
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