title: Production of sex steroid hormones from DHEA in articular chondrocyte of rats.
abstract: Dehydroepiandrosterone (DHEA), a precursor of sex steroid hormones, is synthesized by cholesterol side-chain cleavage cytochrome P-450 and 17alpha-hydroxylase cytochrome P-450 mainly from cholesterol and converted to testosterone and estrogen by 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-HSD, and aromatase cytochrome P-450. Although sex steroid hormones have important effects in the protection of articular cartilage, it is unclear whether articular cartilage has a local steroidogenic enzymatic machinery capable of metabolizing DHEA. This study was aimed to clarify whether steroidogenesis-related enzymes are expressed in articular chondrocytes, whether expression levels are changed by DHEA, and whether articular chondrocytes are capable of synthesizing sex steroid hormones from DHEA. Articular chondrocytes isolated from adult rats were cultured with DHEA for 3 days. All of the mRNA expressions of steroidogenesis-related enzymes were detected in cultured articular chondrocytes of rats, but the mRNA expression levels of testosterone and estradiol in cultured media increased after the addition of DHEA. These findings provided the first evidence that articular chondrocytes expressed steroidogenesis-related enzyme genes and that they are capable of locally synthesizing sex steroid hormones locally from DHEA.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8574, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Mukai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tateishi
authors.forename: Shumpei
authors.initials: S
authors.lastname: Miyakawa
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism*; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024043:Collagen Type II; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme