estrone-sulfate and Uterine-Neoplasms

Plasma ethinylestradiol increases 47.6% when taken with ascorbic acid because of competition in producing sulfate conjugation. Thus the role of sulfates may be important. Serum and urinary estrone sulfate (E1-S) in pregnancy and non-pregnancy were analyzed. Its serum peak during the menstrual cycle was 2.67 +/- 0.37 ng/ml (mean +/- SE) and about ten times that of estradiol-17 beta. E1-S showed lower levels in malignant tissues of breast cancer and endometrial cancer. Increased sulfatase activity in the malignant tissue hydrolyzes E1-S to E1, which may develop the tumors. Serum estradiol 17-sulfate (E2-17-S) in pregnancy was first measured. As E2-17-S decreased, lipid peroxides increased. E2-17-S is converted to 2-OH or 4-OH E2-17-S, which act as lipid peroxide scavengers. Pregnancy-induced hypertension showed lower levels of E2-17-S. In vitro study using the human endothelial cell of the aorta, E2-17-S and 2-OH E2-17-S strongly suppressed lipid peroxidation, which precedes atherosclerotic change.

Topics: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Breast Neoplasms; Estradiol; Estrone; Female; Humans; Lipid Peroxidation; Menstrual Cycle; Middle Aged; Pre-Eclampsia; Pregnancy; Uterine Neoplasms

Estrogens (estrone [E1] and estradiol [E2]), their sulfates and progesterone receptor (PR) were evaluated in patients with uterine leiomyomata nontreated and treated with Decapeptyl (D-Trp6-gonadotropin-releasing hormone [GnRH]; Ipsen Biotech, Paris, France). Estrogen concentrations are very high in the leiomyoma (secretory phase, pg/g tissue [mean +/- SEM]: n = 10; E1: 147 +/- 24; E2: 850 +/- 116; E1-sulfate: 1,668 +/- 808; E2-sulfate: 718 +/- 126). Decapeptyl treatment provokes a significant decrease in E2 and particularly in E1 and E2 sulfates. Progesterone receptors were higher in the leiomyoma than in the myometrium; after a long treatment (3 to 4 months) a significant decrease in both tissues is observed. The decrease provoked by D-Trp6-GnRH on estrogens (unconjugated and sulfates) and in PR in the leiomyoma after long treatment, supports the hypothesis that estrogens are implicated in the cause of these tumors.

Topics: Adult; Antineoplastic Agents; Estradiol; Estrogens; Estrone; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Myometrium; Receptors, Progesterone; Triptorelin Pamoate; Uterine Neoplasms

The growth of uterine leiomyoma is regulated not only by the estrogen levels in blood, but also by estrogen production in the tumor itself. In this study, we investigated both the estrone formation (estrone sulfatase activity) and the transformation from estrone to estrone sulfate (estrone sulfotransferase activity) in human leiomyoma tissue. We compared them with those in the myometrium and endometrial tissues overlying and opposite a uterine leiomyoma node. We also measured the tissue concentrations of estrone, estradiol and estrone sulfate. Estrone sulfatase activity in the uterine leiomyoma was 0.49 +/- 0.08 nmol/h/mg protein (Mean +/- SE), and was lower than that in the myometrial tissue (0.76 +/- 0.09). Moreover, the enzyme activity was higher in the endometrium overlying the leiomyoma node (2.62 +/- 0.29) than in the endometrium opposite to it (2.10 +/- 0.24). On the other hand, estrone sulfotransferase activity in the myoma (20.2 +/- 2.4 pmol/h/mg protein) was higher than in myometrial tissue (16.7 +/- 2.3). The concentrations of estrone and estradiol in leiomyoma tissue were lower than in the tissues surrounding the leiomyoma. The tissue concentration of estrone sulfate was higher in leiomyoma tissues. These results suggest that estrone sulfate is hydrolyzed mainly by estrone sulfatase in the endometrium and myometrium surrounding leiomyoma nodes and the estrone formed may affect the growth of leiomyoma.

Topics: Adult; Alcohol Oxidoreductases; Endometrium; Estradiol; Estrogens; Estrone; Female; Humans; Leiomyoma; Myometrium; Sulfatases; Sulfotransferases; Sulfurtransferases; Uterine Neoplasms

Estrone sulfate (E1-S) in the serum and tissues of patients with breast cancer or endometrial cancer was measured by a direct radioimmunoassay without hydrolysis. The concentration of E1-S in breast cancer tissue was 1.64 +/- 0.28 ng/g wet wt (+/- SE), lower than in surrounding normal breast tissue (4.46 +/- 1.23). Estradiol-17 beta(E2)/E1-S was higher in endometrial cancer tissue than normal endometrial tissue. Estrone sulfatase activity in breast cancer tissue was 0.81 +/- 0.23 nmol/h/mg protein, higher than in surrounding normal breast tissue (0.35 +/- 0.11). These results suggest that E1-S, which is abundant in the peripheral circulation, is hydrolyzed by sulfatase in breast cancer tissue or endometrial cancer tissue and liberates free estrogens, which may stimulate the growth of these malignant tumors.

Topics: Adipose Tissue; Breast Neoplasms; Estradiol; Estrogens, Conjugated (USP); Estrone; Female; Humans; Middle Aged; Radioimmunoassay; Sulfatases; Uterine Neoplasms

The present study was undertaken to assess in vitro the endometrial extraction of natural estrogens. Normal, hyperplastic, and neoplastic endometria were studied. This was accomplished by the use of double isotope, single-injection techniques performed during the extracorporeal perfusion of human isolated uterus. The differential permeability of vascular beds in normal and neoplastic endometrium to estrogens was evaluated. The effects of binding by human serum proteins on estrogen influx into the endometrium were also determined. When protein-free Ringer's solution was used as an injection vehicle, both normal and abnormal endometrium permitted free diffusion of estradiol (E2), estrone (E1), and estrone sulfate (E1S). In contrast, the endometrial extraction of these estrogens from human female serum was significantly lower than that obtained with Ringer's solution. The extraction of E2, E1, and E1S from human serum was significantly higher in hyperplastic and carcinomatous endometria than in normal proliferative endometria. We conclude that 1) membrane permeability to estrogenic influxes differs between normal and abnormal endometria and 2) plasma proteins decrease the endometrial uptake of estrogens.

Topics: Adenocarcinoma; Endometrial Hyperplasia; Endometrium; Estradiol; Estrone; Female; Humans; Perfusion; Uterine Neoplasms; Uterus

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

Exogenous oestrogens are highly effective in relieving not only the acute symptoms of ovarian failure, such as vasomotor instability and vaginal dryness, but also in conserving postmenopausal bone mass. However, the oestrogen doses needed to achieve these benefits also induce endometrial proliferation. The risk of endometrial hyperplasia and carcinoma are thereby increased and unopposed oestrogen therapy is associated with a high incidence of abnormal vaginal bleeding requiring appropriate, invasive investigations. The cost-effectiveness of therapy and patient compliance are likely to be correspondingly reduced. Various strategies have been proposed to try to overcome the risk of endometrial hyperstimulation and these strategies have been reviewed. Based upon the available evidence, progestogen addition appears the most sensible and has been shown to be effective. It is now clear that progestogens should, in sequential therapies, be administered for 12 days each cycle for maximum protection. Concern has been expressed that the regular withdrawal bleed induced by sequential treatment will reduce patient compliance. Progestogens have, therefore, been added in a continuous fashion to try to prevent endometrial proliferation and thereby induce amenorrhoea. The ideal continuous, oestrogen/progestogen regimen has not yet been developed: all those evaluated to date are associated with a high incidence of breakthrough bleeding which is likely to restrict their use. Progestogens can cause undesirable physical, psychological and metabolic effects. The incidence and severity of side-effects will depend upon the type of progestogen prescribed, the route of administration, and the dose. Minimum effective daily doses of certain types of progestogens have now been established in terms of endometrial protection. Regrettably, few data are available on the physical and psychological effects of these progestogen doses: more information is available on lipid and lipoprotein effects but the data are confused and, at times, contradictory. More research is urgently needed to determine which of these progestogens is most suitable for addition to postmenopausal oestrogen therapy.

Topics: Endometrial Hyperplasia; Estradiol; Estriol; Estrogens; Estrogens, Conjugated (USP); Estrone; Female; Humans; Menopause; Progestins; Retrospective Studies; Risk; Uterine Neoplasms

Of the 24 samples of leiomyoma tissues examined 14 were shown to have aromatase activity in vitro. In contrast only 1 of 12 samples of myometrium had any demonstrable activity. Measurements of tissue oestrogen levels showed no correlation with the amount of aromatase activity although oestradiol levels were consistently higher in the tumour tissues compared with the normal myometrium.

Topics: Androstenedione; Aromatase; Estradiol; Estrone; Female; Humans; Leiomyoma; Microbial Collagenase; Myometrium; Oxidoreductases; Uterine Neoplasms

Plasma estrone sulphate ( E1S ) and estrone (E1) concentrations were determined in healthy postmenopausal women and in postmenopausal women with endometrial cancer, matched for body weight, age, and years since menopause. E1S levels (mean +/- SD) were significantly higher (P less than 0.05) in cancer patients with normal weight (511 +/- 200 pg/ml) than in control subjects (303 +/- 99 pg/ml). E1S levels were also higher in obese cancer patients (691 +/- 328 pg/ml) than in obese control subjects (610 +/- 139 pg/ml). Both cancer groups showed similar plasma E1 levels as compared with their respective controls. The E1S /E1 ratio was higher in both groups of cancer patients than in control subjects. These data suggest that estrogen conjugates should be taken into account during studies on estrogen balance and endometrial cancer.

Topics: Aged; Body Weight; Estrone; Female; Humans; Menopause; Middle Aged; Radioimmunoassay; Time Factors; Uterine Neoplasms

The metabolism of [3H] estrone sulfate was studied in endometrial tissue obtained from postmenopausal women with atrophic endometrium (I), benign endometrial proliferative changes (II) and endometrial carcinoma (III) and in perimenopausal women with proliferative (IV) and secretory (V) endometrium. Total hydrolysis (i.e. formation of [3H] estrone + [3H] estradiol-17 beta) of [3H] estrone sulfate as well as formation of [3H] estradiol-17 beta only was significantly less in group I than in the other groups. The formation of [3H] estradiol-17 beta was greater in group V than in the other groups. It is speculated that formation of estradiol-17 beta in the endometrium from estrone sulfate may be of importance in the genesis of endometrial disorders in the postmenopausal woman.

Topics: Aged; Endometrium; Estradiol; Estrone; Female; Humans; Hydrolysis; Menopause; Middle Aged; Progesterone; Uterine Neoplasms

The ability of human endometrium to synthesize estrogen from testosterone (T) was investigated. Normal and malignant endometrial specimens were incubated in a complete nutrient medium with 1 muC/ml (approximately 10 pmol/ml) of [3H]T for 20 hrs. Various estrogens: estrone (E1), estradiol (E2), estrone sulfate (E1S), and estradiol-3-sulfate (E2S) were isolated from cultured tissue and medium. The capacity of aromatization, expressed in pmol of estrogen formed/g of tissue, of proliferative endometria was found to be significantly higher than that of secretory endometria (prol. n=12, 0.53 +/- 0.21, vs sec. n=13, 0.15 +/- 0.09, mean +/- s.d., P less than 0.005). In nine cancer endometrial specimens studied, the estrogen produced varied from 0.3 to 15 pmol/g of tissue. These studies represent the first evidence that human endometrium is capable of synthesizing estrogens from delta 4 androgens at a concentration similar to plasma level. The changes of the capacity of aromatization during the two phases of the menstrual cycle indicate that the estrogen synthesis in endometrium is apparently regulated by hormones. The presence of aromatase in cancer endometria may play an important role in promoting the cell growth in estrogen sensitive endometrial cancer.

Topics: Aromatase; Endometrium; Estradiol; Estrogens; Estrone; Female; Humans; Menstruation; Testosterone; Uterine Neoplasms

In post-menopausal women, the role of Estrone sulphate (E1S) has not been clearly defined, and few data are available in the literature. The present study concerns the plasma E1S levels in post-menopausal women with and without endometrial cancer; the results showed that the E1S levels are related to body size but not to endometrial cancer as the free estrogens.

Topics: Adenocarcinoma; Endometrium; Estrone; Female; Humans; Menopause; Uterine Neoplasms