Reference

Studies on the metabolic fate of dehydroepiandrosterone sulfate

Studies on the metabolic fate of dehydroepiandrosterone sulfate. 2. Metabolism and plasma protein binding in female animals. Midorikawa, Toshifumi; Sato, Akeshi; Sakurai, Shuichi; Fujimoto, Yoshiaki; Nose, Takashi; Tsukamoto, Goro (Pharm. Res. Cent., Kanebo Ltd., Osaka, Japan). Iyakuhin Kenkyu, 8(1), 73-82 (Japanese) 1977. CODEN: IYKEDH. DOCUMENT TYPE: Journal CA Section: 2 (Hormone Pharmacology) The metabolites of 14C-labeled I sulfate [651-48-9] injected i.v. into rats are androstenediol monosulfate [25654-87-9], 7.alpha.-OH-I sulfate [53-00-9], 7.beta.-OH-I sulfate [2487-48-1], and androstenetriol sulfate [12687-31-9] in the urine, and androstenediol disulfate [21861-04-1], 7.alpha.-OH-I sulfate, and 7.beta.-OH-I sulfate, in the bile. The radioactivity assocd. with plasma proteins was .gtoreq. 80% of the given dose at 12 h.

Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1b

Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1b. Dulos, John; Verbraak, Evert; Bagchus, Wilma M.; Boots, Annemieke M. H.; Kaptein, Allard (Organon NV, Oss, Neth.). Arthritis & Rheumatism, 50(10), 3346-3353 (English) 2004 John Wiley & Sons, Inc. CODEN: ARHEAW. ISSN: 0004-3591. DOCUMENT TYPE: Journal CA Section: 15 (Immunochemistry) Objective. The endogenous steroid dehydroepiandrosterone (DHEA) has been reported to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P 450 enzyme CYP7B into 7a-OH-DHEA, which has immunostimulating properties. This study was undertaken to investigate the putative role of CYP7B in arthritis using murine collagen-induced arthritis (CIA), an interleukin-1b (IL-1b)-dependent model.There are some reagents with their cas registry numbers 343850-05-5 and 53-00-9 are used in this study. Methods. DBA/1J mice were immunized and administered a booster with type II collagen. The presence of 7a-OH-DHEA was detd. in both arthritic and nonarthritic joints and the serum of CIA mice by RIA. CYP7B mRNA expression was analyzed in synovial biopsy samples, and in fibroblast-like synoviocytes (FLS) isolated from these synovial biopsy samples, by reverse transcriptase-polymerase chain reaction (RT-PCR). In addn., the regulatory role of IL-1b on CYP7B activity in FLS was detd. using RT-PCR, Western blotting, and high-performance liq. chromatog. Results. In knee joint synovial biopsy samples from arthritic mice, 7a-OH-DHEA levels were 5-fold higher than in nonarthritic mice. Elevated levels of 7a-OH-DHEA were accompanied by an increase in CYP7B mRNA expression and were pos. correlated with disease severity. In serum, no differences in 7a-OH-DHEA levels were obsd. between arthritic and nonarthritic mice. Incubation of FLS with IL-1b resulted in a dose-dependent increase in 7a-OH-DHEA formation. In addn., IL-1b enhanced CYP7B mRNA and CYP7B protein levels in FLS. Conclusion. Disease progression in CIA is correlated with enhanced CYP7B activity, which leads to locally enhanced 7a-OH-DHEA levels. Elevated IL-1b levels within the arthritic joint may regulate this increase in CYP7B activity. .