CORTICOTROPIN-RELEASING HORMONE AND ITS RECEPTOR DISTRIBUTION IN FETAL MEMBRANES AND PLACENTA OF THE RHESUS-MONKEY IN LATE-GESTATION AND LABOR

Maternal plasma corticotropin-Releasing Hormone (CRH) rises from midge station 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 examin ed CRH messenger RNA (mRNA) and peptide expression in fetal membranes and the placenta of 14 pregnant rhesus monkeys (140-161 days gestation al age) using Northern blot analysis, in situ hybridization, and immun ocytochemistry to define the cellular distribution of CRH during the l ast third of pregnancy and in relation to onset of both spontaneous te rm and androstenedione-induced preterm labor. To localize the target t issues for placental CRH, CRH receptor gene expression was also studie d in the fetal membranes and placenta. CRH mRNA in the placenta was of similar molecular size to hypothalamic CRH. Placental CRH mRNA increa sed significantly during both spontaneous term and androstenedione-ind uced preterm labor (P < 0.05). Placental CRH peptide detected by CRH i mmunostaining also increased, matching the changes of CRH mRNA. In sit u hybridization and immunocytochemistry demonstrated that syncytiotrop hoblast cells are the major cell type expressing CRH mRNA and producin g CRH protein. CRH mRNA was not detected in either amnion or chorion. CRH receptor complementary DNA and oligo probes that successfully hybr idized CRH receptor mRNA in the fetal rhesus monkey hypothalamus faile d 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 product ion in the pregnant rhesus monkey. The significant increase in CRH pep tide and mRNA content in both spontaneous term and androstenedione-ind uced preterm labor indicates a role for CRH in the process of parturit ion. The lack of CRH receptor mRNA in either the fetal membranes or th e placenta suggests that placental CRH exerts its action at sites othe r than these tissues.