			Home About us Contact

Estrogen Metabolites (estrogen + metabolite)

Distribution by Scientific Domains

Life Sciences	40%

Selected Abstracts

2-methoxyestradiol-mediated anti-tumor effect increases osteoprotegrin expression in osteosarcoma cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2010
Michaela B. Benedikt
Abstract Osteosarcoma is a bone tumor that frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17,-estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2-ME actions, we studied the effect of 2-ME treatment on OPG gene expression in human osteosarcoma cells. 2-ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2-ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3-, 1.9-, 2.8-, and 2.5-fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2-ME treatment. The effect of 2-ME on osteosarcoma cells was ligand-specific as parent estrogen, 17,-estradiol and a tumorigenic estrogen metabolite, 16,-hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co-treating osteosarcoma cells with OPG protein did not further enhance 2-ME-mediated anti-tumor effects. OPG-released in 2-ME-treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2-ME-mediated anti-proliferative effects in osteosarcoma cells, but rather participates in anti-resorptive functions of 2-ME in bone tumor environment. J. Cell. Biochem. 109: 950,956, 2010. © 2010 Wiley-Liss, Inc. [source]

Biological measurement of estrogenic activity in urine and bile conjugates with the in vitro ER-CALUX reporter gene assay

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2002
Juliette Legler
Abstract Although estrogens are excreted as biologically inactive conjugates, they can be reconverted to an active form, possibly by bacteria. A simple method was developed to deconjugate estrogen metabolites present in human urine and fish bile back to active estrogens by enzymatic hydrolysis with ,-glucuronidase or live Escherichia coli cells. Deconjugated extracts were tested for estrogenic activity in the in vitro stable estrogen receptor,mediated chemical-activated luciferase gene expression (ER-CALUX) assay. Estrogen glucuronides in urine obtained from human males and females were effectively converted to active forms after incubation with ,-glucuronidase or E. coli. The highest estrogenic activity was found in deconjugated metabolites from urine of a pregnant woman, in which levels up to 3,000 nmol estradiol equivalents per liter of urine were found after overnight incubation of urine with E. coli. Bile sampled from male bream and flounder from various freshwater and marine locations was also deconjugated and a good correlation was found between high biliary estrogenic activity and elevated levels of xenoestrogenic activity in surface water as well as in plasma vitellogenin. Therefore, the measurement of deconjugated bile could form a useful (indirect) biomarker for internal dose of xenoestrogens in male fish. [source]

Estrone/17,-estradiol conversion to, and tumor necrosis factor inhibition by, estrogen metabolites in synovial cells of patients with rheumatoid arthritis and patients with osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 10 2009
Martin Schmidt
Objective The role of estrogens in rheumatoid arthritis (RA) is debated since both proinflammatory and antiinflammatory effects have been reported. Important evidence of the dual role of estrogens is conversion to various proinflammatory or antiinflammatory metabolites. This study was undertaken to examine the downstream conversion of estrogens in synovial cells from patients with RA or osteoarthritis (OA). Methods We studied serum levels of estrone, estrone sulfate, and estrone sulfate membrane transporters, intracellular interconversion of estrone and 17,-estradiol, and conversion of estrone/17,-estradiol to various estrogen metabolites in RA and OA synovial cells. The effect of estrogen metabolites on tumor necrosis factor (TNF) secretion was also studied in RA and OA synovial cells. Results Serum levels of estrone sulfate were similar in healthy controls and RA patients. Estrone sulfate transporters were present in synovial tissue. Interconversion of estrone and 17,-estradiol and the expression of converting enzymes of the cytochrome P450 family were similar in RA and OA cells. Using estrone and 17,-estradiol as substrates, RA and OA synovial cells produced 16,-, 4-, and 2-hydroxylated estrogens and their 4- and 2-methylation products. The levels of 16,-hydroxylated estrone/17,-estradiol (16,OH-estrone/16,OH-17,-estradiol) were higher than the levels of all other estrogen metabolites. RA synovial cells produced more 16,OH-estrone than did OA synovial cells. Importantly, the 16,OH estrogens did not inhibit TNF secretion, whereas all other estrogen metabolites had marked inhibitory effects. Conclusion Our findings indicate that precursor estrogens are converted to proinflammatory metabolites, particularly in RA synovial cells. RA synovial cells mainly produce the proproliferative 16,OH-estrone, which, in addition to 16,OH-17,-estradiol, is one of the only 2 estrogens studied that does not inhibit TNF secretion. A preponderance of 16,-hydroxylated estrogens is an unfavorable sign in synovial inflammation. [source]