Corticotropin-releasing hormone receptor type 1 and type 2 mediate differential effects on 15-hydroxy prostaglandin dehydrogenase expression in cultured human chorion trophoblasts.
Throughout gestation, the chorion laeve controls the levels of biologically active prostaglandins (PGs) by its high level of nicotinamide adenine dinucleotide-dependent 15-hydroxy PG dehydrogenase (PGDH). In this study, we investigate the effects mediated by CRH receptors on the expression of PGDH in the chorion. We found that both CRHR1 and CRHR2 were localized in cultured chorion trophoblast cells, with CRH-R1alpha, R1beta, R1c, R1e, and R1f and CRHR2beta isoforms identified in these cells. To block the actions of endogenous CRH and its related peptides, cultured chorion trophoblasts were treated with an increasing concentration of alpha-helical CRH 9-41, the nonselective CRH receptor antagonist, which resulted in decreased mRNA and protein expression as well as the activity of PGDH. To investigate the individual role of CRHR1 and CRHR2, cell cultures were treated with the specific CRHR1 antagonist antalarmin and CRHR2 antagonist astressin2B, respectively. The results showed that antalarmin increased whereas astressin2B decreased mRNA and protein expression as well as the activity of PGDH in chorion cells. When the cells were treated with an exclusive CRHR2 agonist, urocortin II, elevated expression and activity of PGDH was exhibited. However, cells treated with either exogenous CRH or urocortin I showed significantly increased PGDH expression, and these effects could be blocked by astressin2B but not by antalarmin. We suggest that, in chorion trophoblast cells, CRHR1 and CRHR2 mediate divergent effects on PGDH expression, and this may provide a precise regulation of PGs levels from chorion to myometrium during pregnancy.
Gao
Lu
L
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
He
Ping
P
Sha
Jinyan
J
Liu
Chunmin
C
Dai
Ling
L
Hui
Ning
N
Ni
Xin
X
D002478:Cells, Cultured; D002823:Chorion / Q000166:cytology / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology*; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D006727:Hormone Antagonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase