The role of steroid sulfate transporters for placental estrogen synthesis

• Applicant: Professor Dr. Ernst Petzinger (†)
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 152381467

Circulating sulfated steroid hormones are delivered to target tissues via uptake carriers,followed by their reactivation via the catalytic activity of the steroid sulfatase (StS) (“sulfatasepathway”). This pathway will be investigated in vitro with the transport-negative but StS- andaromatase-positive choriocarcinoma cell line JEG-3 by stable transfection of cells with various steroidsulfate carriers including SOAT, OATP2B1, OAT4, and OSCP1. The meaning of each carrier for thecellular capacity to transport and convert free hormones from (radiolabeled) pregnenolone sulfate(PREGS), estron-3-sulfate (E1S), dehydroepiandrosterone sulfate (DHEAS) and 16αOH-DHEAS willbe determined by radiochemical and chemical analytics. A major emphasis will be paid on theprecursors DHEAS and 16αOH-DHEAS either supplied alone or in a mixture together with othersteroid sulfates. The unknown in vivo sublocalization of SOAT in syncytiotrophoblasts will beunraveled by immunohistochemistry with newly generated SOAT antibodies. On a long-termperspective the transporters likely to be involved in the transplacental release of steroids will beanalyzed. For this purpose polarized MDCKII cells will be transfected with SOAT and StS and fluxeswill be measured after cotransfection with the ABC-efflux carrier P-glycoprotein. Here, the release offree hormones via energy-dependent efflux by P-glycoprotein out of the cell layer will be measured intranswell cell cultures.

• DFG Programme: Research Units
• Subproject of: FOR 1369: Sulfated Steroids in Reproduction
• Participating Person: Dr. Bernhard Ugele