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Production of sex steroid hormones from DHEA in articular chondrocyte of rats

¹Doctoral Program of Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba; and ²Biomaterials Center, National Institute for Materials Science, Ibaraki, Japan

Submitted 17 January 2007 ; accepted in final form 18 April 2007

Dehydroepiandrosterone (DHEA), a precursor of sex steroid hormones, is synthesized by cholesterol side-chain cleavage cytochrome P-450 and 17-hydroxylase cytochrome P-450 mainly from cholesterol and converted to testosterone and estrogen by 3-hydroxysteroid dehydrogenase (3-HSD), 17-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.

testosterone; estrogen; dehydroepiandrosterone; steroidogenesis-related enzymes

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