Signal transduction characteristics of the corticotropin-releasing hormone receptors in the feto-placental unit.
Placentally derived CRH plays a major role in the mechanisms controlling human pregnancy and parturition. In this study, we sought to investigate the signal transduction mechanisms of CRH Type-1 receptors in the feto-placental unit. To clarify the signal transduction components in placenta and fetal membranes, we investigated the expression of G proteins and adenylate cyclase. Using the nonhydrolysable photoreactive analog [alpha-32P] GTP-azidoanilide and peptide antisera raised against G protein alpha-subunits, we studied coupling of CRH receptors to G proteins in both placental and fetal membranes. Treatment of placental membranes with human CRH (100 nM) increased the labeling of Gq, Go, and Gz but not Gi and Gs. Treatment of fetal membranes with human CRH (100 nM) increased the labeling of Go and Gq but not Gi, Gs, and Gz. These results were supported by experiments that showed that CRH failed to activate adenylate cyclase in these tissues, but induced an increase in inositol phosphates instead. These findings provide new insights into the components of the signal transduction machinery in both fetal and placental membranes and suggest that CRH Type-1 receptors can couple to different G proteins in different tissues. The physiological significance of these observations remains to be elucidated.
Karteris
E
E
The Sir Quinton Hazel Research Centre for Molecular Medicine, Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.
Grammatopoulos
D
D
Randeva
H
H
Hillhouse
E W
EW
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000502:physiology*; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008969:Molecular Sequence Data; D010920:Placenta / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D007295:Inositol Phosphates; D018019:Receptors, Corticotropin-Releasing Hormone; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases