Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone is an estradiol-responsive tissue. Estrogen withdrawal during the menopause causes loss of bone mass and clinically relevant osteoporosis in a third of all women. Sufficient or impaired local production, as well as degradation of estradiol in cells present in the bone microenvironment might be an important mechanism of rescue or might contribute to the development of osteoporosis, respectively. We therefore investigated aromatase and 17beta-hydroxysteroid dehydrogenase type IV (17beta-HSD IV) expression in osteoblast- and osteoclast-like cells. Aromatase mRNA was increasingly expressed in myeloid THP 1 cells differentiated along the monocyte/phagocyte pathway exploiting vitamin D and either granulocyte-macrophage-stimulating factor (GMCSF) or macrophage-stimulating factor (MCSF). In long-term cultures, when sequentially exposed to vitamin D (days 0-21) and GMCSF (days 5-10) and plated on collagen, the amount of expression of aromatase mRNA steadily increased along with the increasing expression of osteopontin mRNA, alpha(v) integrin mRNA, c-fms (MCSF-receptor) mRNA and multinucleated cells developing. The conversion of estradiol from testosterone (10(-7) M/l) in the supernatants of dishes mirrored changes in aromatase mRNA expression and by day 21 rose to 30,000 ng/10(7) cells/24 h. 17Beta-HSD IV mRNA expression was abundant in undifferentiated THP 1 cells and was decreased to approximately 50% by day 21. Unstimulated SV-40 immortalized fetal osteoblasts did not express aromatase mRNA, but the expression was stimulated by the addition of the phorbol ester phorbol myristate acetate (PMA). Unstimulated osteoblasts from primary cultures did not express aromatase mRNA. Osteoblast-like osteosarcoma cells MG 63 expressed faint levels of aromatase mRNA in contrast to the osteosarcoma cell line HOS 58. 17Beta-HSD IV mRNA was expressed in fetal osteoblasts as well as in osteoblasts from primary culture, MG 63 and HOS 58 cells. In summary, we can show the expression of estradiol metabolizing enzymes in cells which are present in the bone microenvironment. Impaired aromatase expression and/or enhanced expression of 17beta-HSD IV may contribute to the pathogenesis of osteoporosis.
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PMID:Local estradiol metabolism in osteoblast- and osteoclast-like cells. 936 87

For preventing the reduction of bone mass in postmenopausal women, oestrogen replacement is known to be useful and the importance of sex steroids in bone metabolism in both sexes is well established. The presence of steroid-converting-enzyme activities in various osteoblast and osteoblast-like cells has been demonstrated using in vitro culture systems. In the present study, we assessed the expression of messenger ribonucleic acid (mRNA) for aromatase, steroid sulphatase, 5 alpha-reductase, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and 3 beta-HSD by reverse transcription-polymerase chain reaction in the human osteoblast-like cell lines, MG 63 and HOS. Oestrogen, androgen and progesterone receptor mRNAs were also measured. Expression of mRNA for these enzymes and receptors was found in both cell lines without induction. From these and previous findings, we conclude that osteoblast-like cells have the capacity to form biologically potent oestrogens and androgens from peripheral circulating steroids. This may indicate an important role of bone in facilitating hormonal action.
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PMID:Steroid formation in osteoblast-like cells. 951 72

This paper describes for the first time the presence of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity in osteoblast-like cells and investigates its characteristics. 3beta-HSD activity was detected by the formation of androstenedione from [3H]dehydroepiandrosterone (DHEA) in whole cell assays of human osteoblast-like cells, HOS and MG-63. The radiolabeled product, androstenedione, was purified by thin-layer chromatography and identified by recrystallization on admixture with authentic androstenedione to show constant specific activities. The apparent Michaelis constant (Km) for DHEA in HOS was found to be 9.9 microM and that in MG-63 was 80.4 microM. The expression of the 3beta-HSD messenger ribonucleic acid in HOS and MG-63 was demonstrated through a reverse transcription-polymerase chain reaction. The PCR products were confirmed by Southern blot analysis. The existence of 3beta-HSD in osteoblast-like cells indicates that these cells convert delta5 androgens into more biologically active delta4 3-keto steroids. These results, together with the demonstration of other steroid converting enzyme systems, suggest that the osteoblast cells play an important role in facilitating hormonal action in bone tissue.
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PMID:3Beta-hydroxysteroid dehydrogenase activity in human osteoblast-like cells. 962 1