The biological activity of the corticotropin-releasing hormone receptor-adenylate cyclase complex in human myometrium is reduced at the end of pregnancy.
We recently suggested that placentally derived CRH might influence human 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 capacity of this receptor in myometrial tissue obtained from women being delivered electively by cesarian section at term (38-40 weeks gestation) and preterm (30-35 weeks gestation) before the onset of labor. Myometrial membrane suspensions were prepared by differential centrifugation, and the production of cAMP after stimulation with various test substances was measured by RIA. In preterm myometrium, both human CRH and cholera toxin stimulated cAMP production. This effect was significantly reduced in term myometrium. The adenylate cyclase was functionally 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 human pregnant myometrium at term, there is a modification in the coupling mechanisms between CRH receptors and the catalytic component of adenylate cyclase, resulting in a reduction of CRH-stimulated cAMP production.
Grammatopoulos
D
D
Department of Medicine, University of Bristol, Bristol Royal Infirmary, United Kingdom.
Stirrat
G M
GM
Williams
S A
SA
Hillhouse
E W
EW
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009215:Myometrium / Q000378:metabolism*; D037342:Pertussis Toxin; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D018019:Receptors, Corticotropin-Releasing Hormone; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D002772:Cholera Toxin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol