title: Role of protein kinase A in regulating steroid sulfate uptake for estrogen production in human placental choriocarcinoma cells.
abstract: The purpose of this study is to assess the role of the protein kinase A (PKA) in regulating uptake of dehydroepiandrosterone sulfate (DHEAS), an estrogen precursor, by syncytiotrophoblasts. Forskolin, a PKA activator, significantly increased [(3)H]DHEAS uptake and the mRNA expression levels of organic anion transporter (OAT) 4 and CYP19A1 in choriocarcinoma JEG-3 cells, while other steroid sulfate transporters present in the placenta showed no change in expression level. KT5720, a PKA inhibitor, attenuated these effects of forskolin. Accordingly, the PKA pathway appears to play an important role in estrogen synthesis by cooperatively regulating OAT4 and steroidogenic enzymes in syncytiotrophoblasts.
authors: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Electronic address: tomi-ms@pha.keio.ac.jp.
authors: M
authors: M
authors: Tomi
authors: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Y
authors: Y
authors: Miyata
authors: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: S
authors: S
authors: Noguchi
authors: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: S
authors: S
authors: Nishimura
authors: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: T
authors: T
authors: Nishimura
authors: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: E
authors: E
authors: Nakashima
mesh_terms: D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism*; D004967:Estrogens / Q000096:biosynthesis*; D006801:Humans; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D004967:Estrogens; D029362:Organic Anion Transporters, Sodium-Independent; C427207:SLC22A11 protein, human; D019314:Dehydroepiandrosterone Sulfate; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Dehydroepiandrosterone sulfate; Estrogen synthesis; OAT4; Protein kinase A; Syncytiotrophoblast