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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iododesethyl tamoxifen aziridine (I-Tam-Az), an analog of the estrogen receptor-affinity label tamoxifen aziridine (Tam-Az) in which the ethyl group has been replaced by an iodine, has been prepared by two routes: (a) metallation of a bromotriarylethylene system, followed by reaction with iodine, and aziridinylation, and (b) direct iodination of a trimethylstannyl triarylethylene system that is the immediate precursor of I-Tam-Az. The latter method can be used to prepare [125I]I-Tam-Az rapidly and in good yield, both at carrier-added and no-carrier-added levels; specific activities greater than 200 Ci/mmol have been obtained. In competitive radiometric binding assays with the estrogen receptor, I-Tam-Az has an apparent affinity of ca. 20%, equivalent to that of Tam-Az. It also undergoes rapid and selective time-dependent, irreversible binding to the estrogen receptor. [125I]I-Tam-Az reacts covalently with estrogen receptor in uterine cytosol preparations; its attachment is rapid and efficient, but somewhat less selective than that of Tam-Az. Estrogen receptor in intact MCF-7 human breast cancer cells can also be labeled with [125I]I-Tam-Az, and autoradiographic analysis of salt extracts of labeled nuclear estrogen receptor on SDS-polyacrylamide slab gels shows highly selective labeling of a 65K protein. [125I]I-Tam-Az is an efficient, selective affinity label for the estrogen receptor, available at high specific activity, and should be useful in studies on estrogen receptor structure, dynamics, and chromatin interactions.
Steroids
PMID:[125I]iododesethyl tamoxifen aziridine: synthesis and covalent labeling of the estrogen receptor with an iodine-labeled affinity label. 344 83

Research efforts over the past several years have focused on the synthesis of competitive and irreversible aromatase inhibitors and examination of these inhibitors in microsomal preparations, in cell culture, and in vivo. Several 7 alpha-substituted androstenediones have demonstrated high affinity for placental aromatase, with apparent Ki's ranging from 1 to 30 nM. Inactivation of aromatase occurred following incubation with alkylating and enzyme-activated irreversible inhibitors. 7 alpha-(4'-Amino)phenylthio-4-androstene-3,17-dione (7 alpha-APTA) exhibits potent inhibitory activity of aromatase in the MCF-7 human mammary carcinoma cell line with an ED50 of approximately 25 nM. The inhibitor did not bind to the estrogen receptor of the cells in vitro nor induce levels of progesterone receptors in intact cells. In vivo studies of 7 alpha-APTA in the DMBA-induced rat mammary carcinoma model resulted in 80% of the tumors responding completely or partially at doses of 25 and 50 mg/kg body wt/day. Thus, these 7 alpha-substituted steroidal aromatase inhibitors are effective medicinal agents and may be useful for the treatment of estrogen-dependent breast cancer.
Steroids
PMID:7 alpha-substituted androstenediones as effective in vitro and in vivo inhibitors of aromatase. 350 58

Eighty-four tumor samples from 70 women with primary ovarian cancer were assayed for cytosol estrogen (ERc) and progestin (PRc) receptor concentrations and aromatase activity. In addition, 22 of the tumors were studied for their response to the aromatase inhibitor, 4-OH-androstenedione, in a soft agar clonogenic cell assay system. Although aromatase activity was detected in almost all of the primary tumors, this enzyme was barely detectable in the majority of metastatic tumor samples. There was no significant correlation between aromatase activity and either the ERc or PRc content of the tumors, or tumor grade. Of 12 tumors grown successfully in the soft agar culture system, only 1 showed a substantial (greater than 50%) reduction in colony-forming efficiency after exposure to the aromatase inhibitor. These results suggest that local estrogen biosynthesis probably does not play an important role in the majority of epithelial ovarian tumors. However, there may be a small subset of estrogen receptor-positive tumors in which aromatase could provide a local growth stimulus.
Steroids
PMID:Aromatase activity in human ovarian cancer. 350 13

Tumor aromatase has been correlated with clinical response to treatment with aminoglutethimide in patients with estrogen receptor-positive advanced breast cancer. There was a significant positive relationship between aromatase status and likelihood of response to therapy, none of five patients with aromatase-negative tumors responding compared with 11 of 18 having aromatase-positive cancers. Measurement of in vitro aromatase in sequential biopsies of large primary tumors before and during treatment with aminoglutethimide-hydrocortisone showed a marked but paradoxical rise in activity following therapy. Assays of aromatase in adipose tissue from the different quadrants of mastectomy specimens from patients with breast cancer indicate that activity was always higher in quadrants associated with tumor as compared with non-involved quadrants. These results emphasize the importance of local estrogen synthesis within the breast in terms of both the natural history and behavior of breast cancers.
Steroids
PMID:The importance of local synthesis of estrogen within the breast. 350 15

Proestrous mouse plasma and urine were subjected to diethyl ether extraction, enzyme hydrolysis and HPLC separation of estrogen components. Radioimmunoassay of the treated proestrous samples with a broad spectrum anti-estrogen serum failed to detect estradiol-17 beta, estrone or estriol. HPLC chromatograms contained two peaks of immunoreactive and estrogen receptor binding material with polarities between those of estriol and estradiol-17 beta. Similar peaks were detected in HPLC chromatograms of urinary extracts from ovariectomized and ovariectomized-adrenalectomized mice. The least polar of the two peaks produced a mass spectrum identical to that of authentic equol [7-hydroxy-3-(4'-hydroxyphenyl)chroman], a phytoestrogen metabolite. The presence of significant quantities of circulating equol in all strains studied, combined with apparently low plasma levels of endogenous classical estrogens during proestrus, confound attempts to study estrogen secretion in the mouse.
Steroids 1985 Jul
PMID:HPLC separation of anti-estrogen and estrogen receptor binding components of mouse plasma. 383 7

The gamma emitting estrogen [16 alpha-125I]iodoestradiol was administered to 11 patients with ovarian cancer and 1 patient with endometrial cancer. At specific times after the administration of the tracer, portions of the tumor and of control tissues, fat and muscle, were removed and counted. The amount of radioactivity in these tissues was compared to the cytosolic estrogen receptor content of the tumor, measured by Sephadex LH-20 gel filtration, in biopsy specimens taken before the injection of the tracer. There was a strong correlation (p less than 0.005) between the estrogen receptor concentration in the biopsied tumor and the amount of radioactivity in the tumor. There was no correlation between the isotope in the muscle and the tumor receptor, nor between the radioactivity in the tumor and that in fat or muscle. As would be expected for a steroid receptor mediated process, the bulk of the total tissue radioactivity was present in the nuclear compartment of the tumors. This pattern was not observed in the muscle. Furthermore, the nuclear radioactivity in the tumors was positively correlated with the cytosolic estrogen receptor content. These experiments demonstrate that under in vivo conditions this gamma emitting estrogen is concentrated in tumors in a manner that is dependent upon the estrogen receptor. It was also found that the concentrations of radioactivity in the blood were high, producing low tumor to blood ratios. The blood level of isotope was not due to the presence of the unmetabolized steroid, which disappeared from blood rapidly, but was caused by circulating metabolites of the injected steroid. Since the concentration of the isotope in the tumor was dependent upon the estrogen receptor level, it would appear from these experiments that it is theoretically possible to use such compounds to image and monitor tumors that contain estrogen receptors. However, rapid metabolism would seem to preclude the use of 16 alpha-iodoestradiol itself for this purpose. These studies point to the possibility that the synthesis of analogs of 16 alpha-iodoestradiol, sterically protected against inactivation by rapid metabolism, may lead to a radiopharmaceutical agent that would be useful for imaging and monitoring estrogen receptor containing tumors.
Steroids
PMID:Concentration of [16 alpha-125I]iodoestradiol in human ovarian tumors in vivo and correlation with estrogen receptor content. 383 15

As part of a search for estradiol derivatives designed for conjugation to carboxyl or amine functions of anti-cancer agents or suitable derivatives thereof, estradiol analogs with side chains at the C-16 or -17 position were prepared for biological assay. These analogs include several which have a substituted nitrogenous function at C-17. The avidity of some of these analogs for binding to estrogen receptor was found to be of a low order.
Steroids
PMID:Synthesis of some analogs of estradiol. 383 57

The metabolism of 3H-androstenedione (delta 4-A) and 3H-estriol (E3) was studied in 12 human breast tumors. Part of each tumor was analyzed for estrogen receptor content. Aliquots of tumor homogenates were incubated for 2 hr separately with 3H-delta 4-A and 3H-E3 in the presence of appropriate cofactors. No distinct differences emerged in the profiles of the unconjugated metabolites of 3H-delta 4-A, the major compounds in the approximate order of descendence being androsterone, androstanedione, testosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, epiandrosterone, and dihydrotestosterone. One tumor homogenate from an infiltrating lobular carcinoma converted 3H-delta 4-A to glucosiduronate metabolites (11%), of which androsterone, 6.4%; testosterone, 1.6%; and androstanediol, 0.6% predominated. The homogenate of this tumor and two other tumors converted 3H-E3 to 3H-E3-3S. Conversions of E3 to E3-3S in the other tumor homogenates were less than 0.6%. No correlation between receptor content and the capability of the tumor to conjugate delta 4-A or E3 evolved. However, correlations between steroid hormone metabolism and tumor histopathology may exist.
Steroids 1980 Jun
PMID:Conjugation of androgens and estrogens by human breast tumors in vitro. 625 Feb 55

These studies were done to determine if the progesterone-induced estrogen receptor-regulatory factor (ReRF) in hamster uterus is 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), i.e. that rapid loss of nuclear estrogen receptor (Re) might be due to enhanced estradiol oxidation to estrone catalyzed by 17 beta-HSD. Treatment of proestrous hamsters with progesterone (approximately 25 mg/kg BW) for either 2 h or 4 h had no effect on 17 beta-HSD activity measured as the rate of conversion of [6,7-3H]estradiol to [3H]estrone by whole uterine homogenates at 35 degrees C. During this same time interval, progesterone treatment increased the rate of inactivation of the occupied form of nuclear Re as determined during a 30 min incubation of uterine nuclear extract in vitro at 36 degrees C. Since we previously demonstrated that such in vitro Re-inactivating activity represents ReRF, the present studies show that ReRF is not 17 beta-HSD or a modifier of that enzyme.
Steroids 1982 Oct
PMID:Progesterone-induced estrogen receptor-regulatory factor is not 17 beta-hydroxysteroid dehydrogenase. 630 57

Homogenates of human breast tumors were incubated with 3H-androsterone and the percentage conversions to androsterone glucosiduronate were determined. In addition, separate portions of the tumors were analyzed for estrogen receptor (ER) and progesterone receptor (PR) to see whether conjugation and receptor content could be correlated. Sixteen of thirty-two tumor homogenates formed androsterone glucosiduronate (0.03-5.9%) from androsterone. There was no correlation between ER content and glucuronyltransferase activity. Considering the twenty-six malignant mammary tumors, of the fifteen PR positive types, five (one-third) formed the conjugate. In contrast, almost two-thirds (seven of eleven) of the PR negative tumors formed androsterone glucosiduronate. These correlations indicate a trend, but not of statistical significance.
Steroids 1983 Oct
PMID:Glucosiduronidation of androsterone by human breast tumors in vitro in relation to the progesterone receptor content. 643 21


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