FOR 1369:  Sulfated Steroids in Reproduction

• Subject Area: Agriculture, Forestry and Veterinary Medicine
• Term: from 2010 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 152381467

The classical dogma is that steroid hormones must be available in an unbound, free form in order to interact with the respective receptor and to initiate a biological response. Steroid glucuronides and sulfates, which are predominantly formed in the liver or kidney, are generally considered as biologically inactive metabolites intended for elimination. However, in pregnant cows huge amounts of estrone sulfate (E1S) are secretory products of the placenta. Similarly in the stallion and boar the testes secrete large amounts of conjugated estrogens, in particular E1S.
The discovery of the co-localisation of estrogen receptors, estrogen sulfatase and sulfotransferase in the same tissue responsible for estrogen synthesis as shown by the expression of aromatase sheds new light on this situation and gives rise to new hypotheses on the role of conjugated estrogens in reproduction and reproductive diseases. There is increasing evidence that hydrolysis of sulfated estrone and dehydroepiandrosterone catalysed by steroid sulfatase is an important alternative source of precursors for the local supply of estrogens and androgens, respectively.
Thus, in addition to the provision of steroid hormones by the secretory activity of a given cell or gland, a second system controlling the availability of biologically active steroids on the cellular level might be established due to the expression of steroid sulfatase and/or sulfotransferase in certain organs, like the placenta, mammary gland, ovary or the testis. The existence of such a system, however, would also require that sulfoconjugated steroids may penetrate the plasma membrane of a target cell in order to get hydrolysed and to become biologically active.
The fact that - other than free steroids - conjugated steroids will not passively pass the lipid cell membrane barrier, questioned the existence of such a secondary local regulatory system. This situation has changed with the discovery of membrane uptake carriers for sulfoconjugated steroids such as the sodium dependent organic anion transporter (SOAT). SOAT has shown to have high substrate specificity for steroid sulfates and is highly expressed in reproductive tissues such as testis and placenta.
The Research Unit focusses around this hypothesis of a local regulatory system concerning the provision of biologically active steroids by using steroid sulfates as precursors or by targeting biological activity through sulfoconjugation of free steroids. Thus, as a completely new aspect in veterinary reproductive endocrinology, this Research Unit addresses the hydrolysis and transmembrane transport of sulfated steroids as additional levels of control of steroid actions.

• DFG Programme: Research Units

Projects

• DHEAS-Specific Signalling in Cells of the Reproductive System (Applicant Scheiner-Bobis, Georgios )
• Impact of Intrafollicular Sulfated Steroids on Follicular Cells and the Oocyte's Developmental Capacity in Cattle (Applicant Wrenzycki, Christine )
• Membrane transporters for sulfated steroid hormones in the testisand their role for spermatogenesis and fertility (Applicants Fietz, Daniela ;  Geyer, Joachim )
• Role of steroid sulfates in the regulation of steroid hormone biosynthesis (Applicant Bernhardt, Rita )
• Role of Steroid Sulfonation as a Mechanism Controlling the Flow of Substrates through the Cascade of Steroidogenic Enzymes in the Porcine Testis (Applicant Schuler, Gerhard )
• Steroids in Reproduction: LC-MS-MS and GC (-MS) Based Steroidomics (Applicant Wudy, Stefan Alexander )
• The role of steroid sulfate transporters for placental estrogen synthesis (Applicant Petzinger, Ernst )

• Spokesperson: Professor Dr. Martin Bergmann