Many enzymes from the short-chain dehydrogenase/reductase superfamily (SDR) have already been well characterized, particularly those that participate in crucial biochemical reactions in the human body (e.g. 11β-hydroxysteroid dehydrogenase 1, 17β-hydroxysteroid dehydrogenase 1 or carbonyl reductase 1). Several other SDR enzymes are completely or almost completely uncharacterized, such as DHRS1 (also known as SDR19C1). Based on our in silico and experimental approaches, DHRS1 is described as a likely monotopic protein that interacts with the membrane of the endoplasmic reticulum. The highest expression level of DHRS1 protein was observed in human liver and adrenals. The recombinant form of DHRS1 was purified using the detergent n-dodecyl-β-D-maltoside, and DHRS1 was proven to be an NADPH-dependent reductase that is able to catalyse the in vitro reductive conversion of some steroids (estrone, androstene-3,17-dione and cortisone), as well as other endogenous substances and xenobiotics. The expression pattern and enzyme activities fit to a role in steroid and/or xenobiotic metabolism; however, more research is needed to fully clarify the exact biological function of DHRS1.
- MeSH
- dehydrogenasy/reduktasy s krátkým řetězcem metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- estron metabolismus MeSH
- HeLa buňky MeSH
- játra metabolismus MeSH
- kortison metabolismus MeSH
- lidé MeSH
- nadledviny metabolismus MeSH
- nádorové buněčné linie MeSH
- oxidoreduktasy genetika metabolismus MeSH
- rekombinantní proteiny biosyntéza genetika MeSH
- sekvence aminokyselin MeSH
- Sf9 buňky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.
- MeSH
- androgeny metabolismus MeSH
- androstendion metabolismus MeSH
- dehydroepiandrosteron metabolismus MeSH
- dehydroepiandrosteronsulfát metabolismus MeSH
- estradiol metabolismus MeSH
- estron analogy a deriváty metabolismus MeSH
- lidé MeSH
- přenašeče organických aniontů metabolismus MeSH
- testosteron metabolismus MeSH
- trombocyty chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- estradiol analýza krev metabolismus MeSH
- estrogenní substituční terapie MeSH
- estrogeny analýza krev metabolismus MeSH
- estron analýza krev metabolismus MeSH
- lidé MeSH
- menopauza fyziologie krev metabolismus MeSH
- osteokalcin účinky léků krev metabolismus MeSH
- postmenopauzální osteoporóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- MeSH
- androstendion metabolismus MeSH
- estron metabolismus MeSH
- játra metabolismus MeSH
- ledviny metabolismus MeSH
- lidé MeSH
- lidské chromozomy, 16-18 MeSH
- mozek metabolismus MeSH
- nadledviny metabolismus MeSH
- oxidace-redukce MeSH
- plíce metabolismus MeSH
- plod metabolismus MeSH
- pohlavní steroidní hormony metabolismus MeSH
- pregnenolon metabolismus MeSH
- progesteron metabolismus MeSH
- progestiny metabolismus MeSH
- těhotenství MeSH
- testis metabolismus MeSH
- testosteron metabolismus MeSH
- thymus metabolismus MeSH
- trizomie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH