Differential regulation of prostaglandin production mediated by corticotropin-releasing hormone receptor type 1 and type 2 in cultured human placental trophoblasts.
Prostaglandin (PG) production by intrauterine tissues plays a key part in the control of pregnancy and parturition. The present study was to investigate the role of placenta-derived CRH and CRH-related peptides in the regulation of PG synthesis and metabolism. We found that placental trophoblasts expressed both CRH-R1 and CRH-R2. Treatment of cultured placental cells with either a CRH or urocortin I (UCNI) antibody resulted in a significant decrease in PGE2 release. Both CRH and UCNI antibodies significantly decreased mRNA and protein expression of synthetic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2 and increased mRNA and protein expression of 15-hydroxyprostaglandin dehydrogenase (PGDH), the key enzyme of PG metabolism. CRH-R1/-R2 antagonist astressin and CRH-R1 antagonist antalarmin significantly inhibited PGE2 release, whereas CRH-R2 antagonist astressin-2b had no effect on PGE(2) release. Administration of astressin decreased expression of cPLA2 but had no effect on COX-2 expression. Antalarmin reduced cPLA2 and COX-2 expression, whereas astressin-2b did not alter cPLA2 expression but increased COX-2 expression. PGDH expression was enhanced by these three antagonists. Cells treated with exogenous CRH and UCNI showed an increase in PGE(2) release and expression of cPLA2 and COX-2 but a decrease in PGDH expression. UCNII and UCNIII had no effect on PGE2 release but decreased COX-2 and PGDH expression. Our results suggested CRH and CRH-related peptides act on CRH-R1 and CRH-R2 to exert different effects on PG biosynthetic enzymes cPLA2 and COX-2 and thereby modulate output of PGs from placenta, which would be important for controlling pregnancy and parturition.
Gao
Lu
L
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
Lu
Chunmei
C
Xu
Chen
C
Tao
Yi
Y
Cong
Binhai
B
Ni
Xin
X
D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006706:Homeostasis; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D011453:Prostaglandins; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D015232:Dinoprostone