4-hydroxyestradiol and 16-hydroxyestrone

It has been proposed that physiologic levels of estrogens stimulate immune responses whereas androgens suppress inflammatory reactions. Thus, prevalence of synovial androgens relative to estrogens would be favorable in rheumatoid arthritis (RA). We investigated synovial fluid (SF) concentrations of several estrogens and androgens and conversion products of the sex steroid precursor dehydroepiandrosterone (DHEA) in supernatants of mixed synoviocytes.. SF steroid concentrations were measured by high performance liquid chromotography and mass spectrometry in 12 patients with RA and 8 subjects with traumatic knee injury (noninflammatory controls). Conversion of DHEA to downstream hormones was measured by thin-layer chromatography and phosphorimaging detection in 3 patients with RA and 3 patients with osteoarthritis (OA).. Overall, SF concentration of free estrogens tended to be higher in RA patients versus controls (p < 0.06). Molar ratio of free SF estrogens/free SF androgens was elevated in RA compared to controls (1.17 +/- 0.32 vs 0.29 +/- 0.08, without unit; p = 0.017). The free SF concentration of the precursor androstenedione was significantly higher in RA patients than in controls (104.6 +/- 32.6 vs 30.4 +/- 0.4 ng/ml; p = 0.011), and SF estrone the aromatase conversion product of androstenedione was also elevated in RA compared to controls (13.6 +/- 2.6 vs 6.6 +/- 0.8 ng/ml; p = 0.035). The biologically active estrogen derivatives, 16a-hydroxyestrone and 4-hydroxyestradiol, were both higher in RA compared to controls (p = 0.085 and p = 0.044, respectively). In mixed RA synoviocytes, DHEA conversion yielded high local levels of 17beta-estradiol (708 pmol/l = 0.193 ng/ml) compared to testosterone (88 pmol/l = 0.026 ng/ml).. SF levels of estrogens relative to androgens are significantly elevated, while those of androgens are markedly reduced, in patients with RA compared to controls. This imbalance is most probably due to increased aromatase activity. Thus, an available steroid precursor, such as DHEA, may be rapidly converted to proinflammatory estrogens in the synovial tissue, which may in turn stimulate the inflammatory process in patients with RA.

Topics: Adjuvants, Immunologic; Adult; Androgens; Arthritis, Rheumatoid; Dehydroepiandrosterone; Estradiol; Estrogens; Estrogens, Catechol; Estrone; Female; Humans; Hydroxyestrones; Male; Middle Aged; Synovial Fluid; Synovial Membrane

The main goal of our study was to assess estrogen contents of breast tumor tissues, having different estrogen receptor status, in relation to long-term follow-up of patients.. Twenty-one breast cancer cases, all collected from January 1986 to January 1988 at the M. Ascoli Cancer Hospital Centre in Palermo, were included in the study and compared with 6 healthy women as a control group. Average follow-up time of patients was 144 +/- 10 months. The estrogen receptor status of tissues was determined by both ligand binding and immunohistochemical assays. A high performance liquid chromatography-based approach, jointly with gas chromatography/mass spectrometry, was used to identify and measure main estrogens, various hydroxyestrogens, and their methoxy derivatives in both normal and tumor tissues.. Although variable concentrations of hydroxylated estrogens were detected, they consistently accounted for >80% of all of the estrogens. Significantly greater amounts of both 2- and 4-hydroxyestradiol, along with a marked increase of 16 alpha-hydroxyestrone (OHE(1)), were observed in cancer with respect to normal breast tissues. A significant positive association was observed with elevated 16 alpha OHE(1) (P = 0.015) in patients alive, leading to significantly lower (P = 0.043) 2OHE(1):16 alpha OHE(1) ratio values. Conversely, ratio values of 4:2 hydroxy+methoxy estrogens was significantly lower (P = 0.006) in deceased patients. Using cutoff values of 1.2 for 4:2 hydroxy+methoxy ratio and 150 fmol/mg tissue for 16 alpha OHE(1) we achieved a clear-cut separation of patients, with over-cutoff patients having 147 months and under cutoff patients showing only 47 months median survival time (P = 0.00008).. Our data imply that individual hydroxyestrogens may have a distinct role in the onset and the clinical progression of breast cancer, with greater 16 alpha OHE(1) levels being in turn associated to cancer with respect to normal tissues and to a prolonged survival of breast cancer patients.

Topics: Adult; Aged; Binding Sites; Breast Neoplasms; Chromatography, High Pressure Liquid; Estradiol; Estrogens; Estrogens, Catechol; Female; Follow-Up Studies; Humans; Hydroxyestrones; Immunoenzyme Techniques; Middle Aged; Receptors, Estrogen; Survival Rate

Endogenous estrogen metabolism may play an important role in the pathogenesis of hormone-related cancers, most notably breast cancer. Despite the importance of estrogen metabolism, little is known about estrogen metabolite profiles during different phases of the menstrual cycle. This study was performed to evaluate the effects of the menstrual cycle on endogenous estrogen metabolism. Twenty-four-hour urine samples were collected daily during 4 precisely defined phases of the menstrual cycle (early follicular, midfollicular, periovulatory, and midluteal phases) from 6 healthy premenopausal women. Urine samples were analyzed for 15 endogenous estrogens and their metabolites by an ion exchange chromatography and the capillary gas chromatography-mass spectrometry method. The patterns of urinary estrogen metabolites (including potentially genotoxic 16alpha-hydroxyestrone, 4-hydroxyestradiol, and 4-hydroxyestrone) followed those of plasma estradiol and estrone, showing significant increases in the periovulatory and midluteal phases. Compared to the early and midfollicular phases, the ratios of 2-hydroxyestrogens/16alpha-hydroxyestrogens and 2-hydroxyestrogens/4-hydroxyestrogens were significantly increased during the periovulatory and midluteal phases (by 28% and 72%, respectively; P < 0.05), suggesting that estrogen metabolism is significantly affected by menstrual cycle phase. These data indicate that menstrual cycle phase must be considered in studies of estrogen metabolism in premenopausal women.

Topics: Adult; Body Weight; Diet; Estradiol; Estrogens; Estrogens, Catechol; Estrone; Female; Follicular Phase; Gas Chromatography-Mass Spectrometry; Humans; Hydroxyestrones; Luteal Phase; Menstruation; Ovulation