The role of steroid sulfate transporters for placental estrogen synthesis
Final Report Abstract
In this project, the steroid sulfate carrier SOAT was localized to syncytiotrophoblast cells and vessel endothelium in third trimester placenta by IHC, ISH and semi-qualitative RT-PCR after LACP. Furthermore, the steroid sulfate carriers SOAT, OAT4 and NTCP were identified as carriers for 16α- OH-DHEAS revealing Michaelis-Menten equations with Km values of 23.1 ± 5.1 µM for OAT4, 319.0 ± 59.5 µM for SOAT, and 51.4 ± 9.9 µM for NTCP. As SOAT is located in vessel endothelial cells this carrier might mediate uptake of 16α-OH-DHEAS from fetal blood while uptake into syncytiotrophoblasts might be mediated by OAT4 which is expressed at the basal membrane side of syncytiotrophoblasts. Localization of SOAT at the apical membrane side of syncytiotrophoblasts could indicate a role for this carrier for supply with C-19 precursors like DHEAS from maternal blood. Our stably transfected SOAT, OATP2B1 and OAT4-JEG-3 cells were expected to have increased uptake capacities of sulfated steroids compared to untransfected JEG-3 FRT control cells and to produce higher amounts of estradiol when incubated with DHEAS. Both assumptions were not confirmed in our measurements. Transport measurements of carrier transfected cells showed similar uptake capacities compared to non-transfected cells. Furthermore, in OATP2B1-JEG-3 cells estradiol synthesis was slightly increased compared to JEG-3 FRT cells, whereas SOAT-JEG-3 cells had impaired estradiol production.
Publications
- (2012) Characerization of JEG-3 cells as in vitro model for the role of steroid sulfate transporters for placental estrogen synthesis. 55th Symposium of the German Society for Endocrinology, Mannheim, March 07-10, 2012. Abstract-CD 55, ISSN 1862- 1503. Prize by the German Society of Endocrinology
Schweigmann H, Grosser G, Galuska CE, Hartmann MF, Alber J, Ugele B, Wudy SA, Geyer J, Petzinger E
- (2012) JEG-3 cells as in vitro model for studies on placental steroid sulfate uptake and estrogen biosynthesis. 8th Transport Colloquium at Castle Rauischholzhausen, Rauischholzhausen, May 17-18, 2012
Schweigmann H, Grosser G, Galuska CE, Hartmann MF, Ugele B, Wudy SA, Geyer J, Petzinger E
- (2012) Role of the sodium-dependent organic anion transporter (SOAT) for placental estrogen synthesis. 78th annual conference of the German Society for Experimental and Clinical Pharmacology and Toxicology, Dresden, March 19-22, 2012. Abstract in Naunyn-Schmiedeberg´s Arch Pharmacol 385 (1): 31
Grosser G, Schweigmann H, Galuska CE, Hartmann MF, Alber J, Funk K, Ugele B, Wudy SA, Geyer J, Petzinger E
- (2012) Steroid sulfate uptake and estrogen biosynthesis in the human placenta. 5th Annual Conference of the International Giessen Graduate Centre for the Life Sciences (GGL), Giessen, September 18-19, 2012
Schweigmann H, Grosser G, Galuska CE, Hartmann MF, Ugele B, Wudy SA, Geyer J, Petzinger E
