title: Role of human chorionic gonadotropin in maintaining 11beta-hydroxysteroid dehydrogenase type 2 expression in human placental syncytiotrophoblasts.
abstract: Proper glucocorticoid exposure in utero is vital for normal fetal organ maturation, but excess glucocorticoids are detrimental to fetal growth and can even predispose the individuals to the high risk of having certain diseases in adulthood. The fetus is protected from 10 times higher maternal glucocorticoid levels by the placental enzyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), which converts biologically active cortisol to inactive cortisone. Thus it is of primary importance to understand how this enzyme is regulated. Activation of cAMP/PKA pathway is known to upregulate 11beta-HSD2 expression in placental syncytiotrophoblasts, however the endogenous hormones utilizing this pathway remain largely unknown. By using cultured human placental syncytiotrophoblasts, we demonstrated that inhibition of protein kinase A with H89 attenuated 11beta-HSD2 expression in the syncytiotrophoblasts, suggesting endogenous factors from the syncytiotrophoblasts using this pathway to maintain 11beta-HSD2 expression in the syncytiotrophoblasts. Neutralization of human chorionic gonadotropin (hCG) secreted by the syncytiotrophoblasts with hCG antibody decreased 11beta-HSD2 promoter activity, mRNA and protein expression as well as intracellular cAMP level, while treatment of the syncytiotrophoblasts with exogenous hCG increased 11beta-HSD2 expression, which was attenuated by H89. Furthermore, we found that cortisol increased both hCG expression and secretion. The up-regulation of 11beta-HSD2 expression by cortisol was significantly attenuated by co-treatment with hCG antibody or H89 in the syncytiotrophoblasts. In conclusion, hCG is an important paracrine or autocrine hormone maintaining 11beta-HSD2 expression and the up-regulation of 11beta-HSD2 expression by cortisol may be mediated in part by hCG in the syncytiotrophoblasts.
authors.affiliation: Shanghai First Maternity and Infant Health Hospital, Tongji University, Shanghai 200040, PR China.
authors.forename: X T
authors.initials: XT
authors.lastname: Ni
authors.forename: T
authors.initials: T
authors.lastname: Duan
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: C M
authors.initials: CM
authors.lastname: Guo
authors.forename: J N
authors.initials: JN
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Sun
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000502:physiology*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D015292:Glycoprotein Hormones, alpha Subunit; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D005576:Colforsin; D003513:Cycloheximide; D000242:Cyclic AMP; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D006854:Hydrocortisone