estrone-sulfate and Ovarian-Neoplasms

Elevated serum levels of 17beta-estradiol (E2) are frequently found in postmenopausal women with ovarian tumors not classified as estrogen-producing. Conversion of circulating estrone sulfate (E1S) to E2 is one alternative way of E2 formation in target tissues in postmenopausal women. Our aim was to find out if conversion of circulating E1S to E2 by the tumor tissue could be a reason for elevated serum E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.. Serum E2 was measured in 12 postmenopausal women with 'non-estrogen-producing' ovarian tumors (nine benign, three malignant). Total hydrolysis of and [3H]E2 formation from [3H]E1S by the tumor tissue homogenates was studied in vitro.. Serum E2 showed significant positive correlations with total hydrolysis of and [3H]E2 formation from [3H]E1S in the total material as well as in the benign tumor subgroup. [3H]E2 formation was the most important independent variable.. Conversion of circulating E1S to E2 by the tumor tissue could be one important reason for elevated S-E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.

Topics: Estradiol; Estrone; Female; Humans; Middle Aged; Ovarian Neoplasms; Postmenopause

The metabolism of [3H]estrone sulfate (E1S) into [3H]estrone (E1) and [3H]estradiol-17 beta (E2) was studied in samples of endometriotic tissue and uterine endometrium obtained simultaneously from 13 patients, 7 in the proliferative and 5 in the secretory cycle phase, and 1 menstruating. E1S was efficiently converted into E1 and E2 by both types of tissue. Total hydrolysis (formation of E1 + E2), as well as the specific formation of E2, was higher in uterine endometrium than in endometriotic tissue, especially in the proliferative phase. Cycle phase associated variations in E2 formation occurred in both tissues, but were statistically significant only for uterine endometrium. E2 formation and total hydrolysis were correlated in endometriotic tissue, but not in uterine endometrium, indicating certain differences in the regulation of estrogen metabolism.

Topics: Endometriosis; Endometrium; Estradiol; Estrogens, Conjugated (USP); Estrone; Female; Humans; In Vitro Techniques; Menstrual Cycle; Ovarian Neoplasms

The enzymatic hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroisoandrosterone, respectively, was studied in cells that were derived from four different malignant tumors of the lower reproductive tract of women, viz. a squamous cell vaginal carcinoma, an ovarian carcinoma, and two endometrial adenocarcinomas. These cells had the capacity to hydrolyze both steroid sulfoconjugates. Estrone sulfate was more efficient as a substrate than dehydroepiandrosterone sulfate, since the amount of product formed from estrone sulfate was approximately 3-fold greater than that formed from dehydroepiandrosterone sulfate. Some kinetic parameters of steroid sulfatase were determined in the four cell types and were found to be very similar, as were the rates of hydrolysis. Sulfatase activity was linear with incubation time for at least 2 h and with cell number up to 3.2 X 10(6) cells/mL. The apparent pH optimum of steroid sulfatase, determined by the use of cell sonicates and estrone sulfate as the substrate, was between 6.0 and 7.5. The apparent Km values of steroid sulfatase for estrone sulfate in both squamous vaginal carcinoma cells and ovarian carcinoma cells were both 5 microM, and those for dehydroepiandrosterone sulfate in squamous vaginal carcinoma cells and endometrial adenocarcinoma cells were 6 and 4 microM, respectively. The optimal temperature of steroid sulfatase in squamous vaginal carcinoma cells was 50 C; at this temperature, enzymatic activity was more than twice that at 37 C. The steroid sulfatase pathway that is operative in carcinoma cells in vitro to produce free steroids from steroid sulfate precursors also may serve to produce free steroids in vaginal, endometrial, and ovarian carcinomas in vivo and, perhaps, maintain and stimulate tumor growth.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Line; Cystadenocarcinoma; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estrone; Female; Humans; Hydrolysis; Ovarian Neoplasms; Steryl-Sulfatase; Sulfatases; Uterine Neoplasms; Vaginal Neoplasms