title: Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.
abstract: 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.
authors.affiliation: Changning Maternity and Infant Health Hospital, Shanghai, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Shu
authors.affiliation: Changning Maternity and Infant Health Hospital, Shanghai, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jianneng
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Wangsheng
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis*; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D016329:Sp1 Transcription Factor; D000242:Cyclic AMP; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D020928:Mitogen-Activated Protein Kinases