THE BIOLOGICAL-ACTIVITY OF THE CORTICOTROPIN-RELEASING HORMONE RECEPTOR-ADENYLATE CYCLASE COMPLEX IN HUMAN MYOMETRIUM IS REDUCED AT THE ENDOF PREGNANCY

We recently suggested that placentally derived CRH might influence hum an parturition via specific receptor mechanisms. We identified a human myometrial CRH receptor that changes to a high affinity state in the later stages of pregnancy and becomes coupled to the adenylate cyclase system. The purpose of this study was to investigate the functional c apacity of this receptor in myometrial tissue obtained from women bein g delivered electively by cesarian section at term (38-40 weeks gestat ion) and preterm (30-35 weeks gestation) before the onset of labor. My ometrial membrane suspensions mere prepared by differential centrifuga tion, and the production of cAMP after stimulation with various test s ubstances was measured by RIA. In preterm myometrium, both human CRH a nd cholera toxin stimulated cAMP production. This effect was significa ntly reduced in term myometrium. The adenylate cyclase was functionall y active in term myometrium, as demonstrated by the use of forskolin. Furthermore, pertussis toxin pretreatment of term myometrial membranes did not increase the response to CRH. These results suggest that in h uman pregnant myometrium at term, there is a modification in the coupl ing mechanisms between CRH receptors and the catalytic component of ad enylate cyclase, resulting in a reduction of CRH-stimulated cAMP produ ction.