Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conceptus estrogen synthesis in the pig begins with the d 11 blastocyst and continues throughout pregnancy. Estrogens have been implicated as regulators of numerous in utero events related to conceptus survival and development. Studies conducted in our laboratory indicate that progesterone (P4) production by the porcine placenta increases steadily throughout gestation. Estrone (E1) production is triphasic with peaks between d 14-18, around d 30, and a sustained increase from d 70 until parturition. Addition of pregnenolone (P5) augments in vitro P4 and E1 production by both the placenta and the endometrium. Both estrogen concentrations and the ratio between conjugated and free estrogens change drastically during gestation. Evidence from our laboratory suggests that enhanced and prolonged sulfatase activity by d 90 of gestation, coupled with an increase in sulfatase activity-not a change in aromatase activity-contributes to the rise in free estrogens as parturition approaches. We assessed the relative importance of ovarian versus placental production of P4 as a mediator of prenatal survival, conceptus development, and steroidogenesis by the placenta and endometrium. Among other findings, exogenous administration of the non-aromatizable progestagen medroxyprogesterone acetate (MPA) to ovariectomized (OVX) gilts between either d 20-30 or d 60-70 of gestation did not adversely affect concepts survival or development, in vivo estrogen measurements, or in vitro placental steroidogenesis. We also demonstrated that pregnancy may also be maintained during d 20-30 and d 60-70 in OVX gilts administered large quantities of P5 exogenously, presumably due to placental P4 production. Recent studies have examined variables of region of the placenta and intrauterine position on conceptus development, and placental and endometrial steroidogenesis under normal and crowded intrauterine conditions. Results indicated 1) a differential release of P4 and E1 by different regions of the placenta at certain days of gestation, 2) no compensatory increase in steroidogenic activity of the pig placenta when total placental mass was reduced, and 3) a less pronounced effect of intrauterine position on steroidogenic activity in the pig compared with other litter-bearing species.
...
PMID:Aspects of placental estrogen synthesis in the pig. 799 37

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.
...
PMID:Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells. 847 61

This report concerns the evaluation of various estrogens, estrone (El), estradiol (E2), and estrone sulfate (E1S), as well as E1S-sulfatase and aromatase activities in pre- and postmenopausal women with breast cancer. The levels (in picomoles per g; mean +/- SEM) of the various estrogens in the breast tissue from premenopausal patients (n = 11) are: El, 1.4 +/- 0.5; E2, 1.2 +/- 0.6; and E1S, 1.2 +/- 0.3. In postmenopausal patients (n = 23), the values are, respectively, 1.0 +/- 0.4, 1.4 +/- 0.7, and 3.3 +/- 1.9. These concentrations of estrogens in the tumors of postmenopausal patients are significantly higher than those found in plasma. The activity of E1S-sulfatase in both pre- and postmenopausal patients was 50-200 times higher than that of aromatase. E1S-sulfatase and aromatase activities are significantly higher in post-menopausal than in cycling patients. It is concluded that despite the low levels of circulating estrogens in postmenopausal patients, the tissue concentrations of these steroids are several-fold higher than those in plasma, suggesting tumor accumulation of these estrogens. The physiopathology and clinical significance of these high levels of the various estrogens (E1, E2, and E1S) as well as sulfatase and aromatase activities in postmenopausal patients with breast cancer is yet to be explored.
...
PMID:Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients. 863 51

In the present studies, the concentrations (mammary tissue and plasma) of estrone (E1), estradiol (E2) and their sulfates (E1S and E2S), as well as the sulfatase and aromatase activities, were evaluated in patients with breast fibroadenomas. Comparative studies of the evaluation of these parameters were carried out in: (A) tumor tissue, (B) areas surrounding the tumor and (C) areas distant from the tumor (glandular tissue) considered as normal tissue. The concentrations in the tumor tissue (in pmol/g tissue) of E1, E2 and E1S were significantly higher (2-3 times) than in the area of the breast considered as normal. Sulfatase and aromatase activities were found in the breast fibroadenoma tissue. Sulfatase activity was much higher than aromatase (30-150 times) and sulfatase levels were significantly higher in the fibroadenoma tissue than in the area considered as normal. Plasma evaluation of E1, E2, E1S and E2S concentrations showed no significant differences in relation to those of healthy control women. In conclusion, the high levels of estrogens and their sulfates, as well as the enzymes involved in estrogen formation--sulfatase and aromatase in breast fibroadenoma--contribute to the hypothesis that this disease may be hormone-dependent.
...
PMID:Concentrations of estrone, estradiol and their sulfates, and evaluation of sulfatase and aromatase activities in patients with breast fibroadenoma. 909 42

In human estrogen-dependent neoplasms such as breast, endometrioid endometrial, and surface epithelial-stromal ovarian carcinomas, intratumoral aromatase is considered to play important roles in converting circulating androgens derived from adrenal cortex and/or ovary to estrogens, possibly in association with 17 beta-HSD type 1 and estrogen sulfatase. Analysis of intratumoral aromatase in these estrogen-dependent neoplasms is important not only in understanding the development and biological behavior of these tumors, but also in the clinical management of these patients, because suppression of intratumoral aromatase by newly developed aromatase inhibitors may provide new potentials in endocrine therapy of these patients.
...
PMID:Intratumoral aromatase in human breast, endometrial, and ovarian malignancies. 979 59

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10-50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.
...
PMID:Determinants of tissue estradiol levels and biologic responsiveness in breast tumors. 979 11

The importance of estrogens in bone metabolism is illustrated by the accelerated bone loss and increase in osteoporotic fractures associated with postmenopausal estrogen deficiency. In this study, the expression and activity of the enzymes involved in estrogen metabolism in human osteoblastic cells were investigated in relation to differentiation of these cells. PCR reactions using mRNA from an in vitro differentiating human cell line (SV-HFO) were performed to assess mRNA expression of the enzymes aromatase, different subtypes of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and steroid sulfatase. Aromatase, sulfatase, and 17beta-HSD type 2 and 4 were found to be expressed throughout differentiation. Expression of 17beta-HSD type 3, however, was relatively weak, except for early time points in differentiation. Type 1 17beta-HSD expression was not detected. Aromatase activity decreased during differentiation, as was demonstrated by the conversion of androstenedione (A) and testosterone (T) into estrone (E(1)) and estradiol (E(2)), respectively. The 17beta-HSD isozymes catalysing a reductive reaction convert androstenedione and estrone into testosterone and estradiol, respectively. Their activity declined with differentiation. Analysis of 17beta-HSD activity indicated both oxidative (E(2) to E(1); T to A) and reductive (E(1) to E(2); A to T) metabolism at all stages of osteoblast differentiation. Both activities declined as cells moved toward a differentiating mineralizing phenotype. However, the oxidative reaction was increasingly in favor of the reductive reaction at all times during differentiation. Sulfatase activity, as demonstrated by the conversion of estrone-sulfate into estrone, was constant during differentiation. In conclusion, we have demonstrated that all enzymes necessary for estrogen metabolism are expressed and biologically active in differentiating human osteoblasts. The activity of aromatase and 17beta-HSD was found to be dependent on the stage of cell differentiation. In addition, human osteoblasts effectively convert estradiol into estrone. The efficacy of osteoblasts to synthesize estradiol may determine the ultimate change in rate of bone turnover after menopause, as well as the development of osteoporosis. Moreover, the enzymes involved in the metabolism of estradiol may form a target for intervention.
...
PMID:Estradiol formation by human osteoblasts via multiple pathways: relation with osteoblast function. 1053 74

From an edible mushroom Lepiota americana Pk., (Agaricaceae), 2-aminophenoxazin-3-one that inhibited aromatase at IC50 = 5.7 microM and 3 beta-hydroxy-5,8-epidioxyergosta-6,22-diene that inhibited sulfatase at IC50 = 0.9 microM were isolated. Neither 2-aminophenoxazin-3-one was active against sulfatase nor was 3 beta-hydroxy-5,8-epidioxyergosta-6,22-diene active against aromatase.
...
PMID:Aromatase and sulfatase inhibitors from Lepiota americana. 1070 43

In the present study, the concentrations of estrone (E(1)), estradiol (E(2)) and their sulfates (E(1)S and E(2)S), as well as the sulfatase and aromatase activities, were evaluated in post-menopausal patients with breast cancer. Comparative studies of the evaluation of these parameters were carried out in (a) tumor tissue, (b) areas surrounding the tumor, and (c) areas distant from the tumor (glandular tissue) which were considered as normal tissue. The levels (in pm/g; mean +/- SEM) were: for E(1) in the (a) area: 320+/-95; in (b): 232+/-86; and in (c): 203+/-71; for E(2) in the (a) area: 388+/-106; in (b): 224+/-48; and in (c): 172+/-80; for E(1)S in the (a) area: 454+/-110; in (b): 259+/-90; and in (c): 237+/-65; for E(2)S in the (a) area:318+/-67; in (b): 261+/-72; and in (c): 232+/-75, respectively. The values of E(1)S and E(2) were significantly higher in the tumor tissue than in the area considered as normal. In all the tissues studied, the sulfatase activity was much higher than aromatase (130-200). In addition, the sulfatase levels were significantly higher in the peripheral and in the tumor tissue than in the area considered as normal. The levels of aromatase were significantly higher in tumoral than in normal tissue. The present data extend the "intracrine concept" for breast cancer tumors. The physiopathology and clinical significance as promoter parameters in breast cancer is to be explored.
...
PMID:Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. 1073 34

Human breast cancer tissue contains all the enzymes (estrone sulfatase, 17 beta-hydroxysteroid dehydrogenase, aromatase) involved in the last steps of estradiol biosynthesis. This tissue also contains sulfotransferase for the formation of the biologically inactive estrogen sulfates. In the past years, it has been demonstrated that various progestins (promegestone, nomegestrol acetate, medrogestone) as well as tibolone and its metabolites are potent inhibitors of sulfatase and 17 beta-hydroxysteroid dehydrogenase activities. It was also shown that medrogestone, nomegestrol acetate, promegestone or tibolone can stimulate the sulfotransferase activity for the local production of estrogen sulfates. All these data, in addition to numerous agents which can block the aromatase action, lead to the new concept of Selective Estrogen Enzyme Modulators (SEEM) which can largely apply to breast cancer tissue. The exploration of various progestins and other active agents in trials with breast cancer patients, showing an inhibitory effect on sulfatase and 17 beta-hydroxysteroid dehydrogenase, or a stimulatory effect on sulfotransferase, will provide a new option in the treatment of this disease.
...
PMID:The SEEM: selective estrogen enzyme modulators in breast cancer. 1086 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---