Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts

Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (h...

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Veröffentlicht in:PloS one 2014-09, Vol.9 (9), p.e107938
Hauptverfasser: Shu, Qun, Li, Wenjiao, Li, Jianneng, Wang, Wangsheng, Liu, Chao, Sun, Kang
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Wang, Wangsheng
Liu, Chao
Sun, Kang
description Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.
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The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0107938</identifier><identifier>PMID: 25229504</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>11-beta-Hydroxysteroid Dehydrogenase Type 2 - biosynthesis ; 11β-Hydroxysteroid dehydrogenase ; Activation ; Apoptosis ; Binding sites ; Biology and Life Sciences ; Cascades ; Chorionic gonadotropin ; Chorionic Gonadotropin - pharmacology ; Chorionic gonadotropins ; Consent ; Cyclic AMP ; Cyclic AMP - chemistry ; Cyclic AMP - metabolism ; Cyclic AMP - pharmacology ; Dehydrogenases ; Enzyme Induction - drug effects ; Extracellular signal-regulated kinase ; Female ; Fetuses ; Gestation ; Glucocorticoids ; Glycoproteins ; Gonadotropins ; Hospitals ; Humans ; Inhibition ; Kinases ; Life sciences ; MAP kinase ; MAP Kinase Signaling System - drug effects ; Medicine and Health Sciences ; Mitogen-Activated Protein Kinases - metabolism ; mRNA ; Pathways ; Phosphorylation ; Phosphorylation - drug effects ; Pituitary (anterior) ; Placenta ; Pregnancy ; Protein kinase ; Proteins ; RNA ; Rodents ; Signal transduction ; Sp1 Transcription Factor - metabolism ; Trophoblasts ; Trophoblasts - cytology ; Trophoblasts - drug effects ; Trophoblasts - metabolism</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e107938</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Shu et al. 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The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. 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The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25229504</pmid><doi>10.1371/journal.pone.0107938</doi><oa>free_for_read</oa></addata></record>
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subjects 11-beta-Hydroxysteroid Dehydrogenase Type 2 - biosynthesis
11β-Hydroxysteroid dehydrogenase
Activation
Apoptosis
Binding sites
Biology and Life Sciences
Cascades
Chorionic gonadotropin
Chorionic Gonadotropin - pharmacology
Chorionic gonadotropins
Consent
Cyclic AMP
Cyclic AMP - chemistry
Cyclic AMP - metabolism
Cyclic AMP - pharmacology
Dehydrogenases
Enzyme Induction - drug effects
Extracellular signal-regulated kinase
Female
Fetuses
Gestation
Glucocorticoids
Glycoproteins
Gonadotropins
Hospitals
Humans
Inhibition
Kinases
Life sciences
MAP kinase
MAP Kinase Signaling System - drug effects
Medicine and Health Sciences
Mitogen-Activated Protein Kinases - metabolism
mRNA
Pathways
Phosphorylation
Phosphorylation - drug effects
Pituitary (anterior)
Placenta
Pregnancy
Protein kinase
Proteins
RNA
Rodents
Signal transduction
Sp1 Transcription Factor - metabolism
Trophoblasts
Trophoblasts - cytology
Trophoblasts - drug effects
Trophoblasts - metabolism
title Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts
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