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

Steroid delta 4-5 alpha- and delta 4-5 beta-reductase activity was determined in 16 human mammary tumors and 8 DMBA-induced rat mammary tumors using a spectrophotometric assay. Steroid delta 4-5 alpha-reductase was present in all tumors investigated while delta 4-5 beta-reductase was detected in only 6 estrogen receptor negative human breast tumors and absent in all estrogen receptor positive human breast tumors as well as in all rat mammary tumors. Further support for the presence of delta 4-5 beta-reductase was established by using a dual-labelling technique consisting of incubating tumor slices with [14C] testosterone and adding [3H] etiocholanolone, [3H] testosterone and [3H]-5 alpha-dihydrotestosterone at the end of the reaction. Following extraction and chromic acid oxidation, 4-androstenedione, 5 beta-androstanedione and 5 alpha-androstanedione were isolated and purified, and the constancy of the 14C/3H ratio was used as proof of 5 alpha-reductase and 5 beta-reductase. These results were shown to be consistent with the data obtained using the spectrophotometric assay.
Steroids 1979 Jan
PMID:Steroid delta 4-5 beta-reductase in human mammary tumors. 10 50

The ability of human mammary tumors to convert 7alpha 3H-testerone to estrogens was examined in order to determine whether this bore any relationship to estrogen receptor and steroid sulfurylation levels; such levels being indicative of hormone dependency. In 8 out of 9 tumors, formation of estradiol-17beta from testosterone was demonstrated. Those tumors showing the lowest conversion of testosterone to estradiol-17beta possessed the highest levels of dehydroepiandrosterone sulfotransferase which lends support to data implicating sulfurylation in the regulation of steroid metabolism in human tumors. All tumors activated sulfate to adenosine-3'-phospho-5'-phosphosulfate and the concentrations were significantly correlated withe the recorded levels of dehydroepiandrosterone sulfate. Estrogen receptor levels did not show any obvious relationship to the other parameters.
Steroids 1976 Oct
PMID:Steroid metabolism by human mammary carcinoma. 13 57

The high concentrations of dehydroepiandrosterone and its 3beta-sulfate in the blood are potential preocursors for further metabolism by normal and tumorous human mammary tissue. In vitro metabolism of 7n-3H- and 1,2,6,7(n)-3H-dehydroepiandrosterone by fifteen mammary tumors was examined. Some 10--50% of the radioactivity recovered was in the form of 7-oxygenated derivatives: the major metabolite being 7alpha-hydroxydehydroepiandrosterone accompanied by lesser amounts of the 7beta-epimer. 5-Androstene-3beta,17beta-diol was formed in all but one case. Evidence showed that the high yield of 7alpha-hydroxy derivative resulted from direct action of a 7alpha-hydroxylase capable of using both dehydroepiandrosterone and 5-androstene-3beta,17beta-diol as substrates. Although 5-androstene-3beta,17beta-diol competed with estradiol-17beta for the estrogen receptor, this property was considerably reduced as a consequence of the introduction of a 7alpha-hydroxyl or 16alpha-hydroxyl group. Dehydroepiandrosterone, which competed less effectively for the estrogen receptor site, showed almost no affinity for the site upon the introduction of a 7alhpa-hydrocyl group. A regulatory role for the 7alpha-hydroxylase is outlined.
Steroids 1978 Jan
PMID:Products of dehydroepiandrosterone metabolism by human mammary tumors and their influence on estradiol receptor binding. 14 1

The metabolism of 7-(3)H-pregnenolone was studied in vitro using 16 human breast carcinomas. All mammary tumors transformed pregnenolone to progesterone. All estrogen receptor poor tumors and 4 out of 8 estrogen receptor rich tumors converted pregnenolone to 17-hydroxypregnenolone. Five estrogen receptor poor tumors showed the presence of 17,20-lyase as evidenced by formation of dehydroepiandrosterone and androstenedione. In two estrogen receptor poor tumors, conversions of pregnenolone to progesterone, 17-hydroxy pregnenolone, dehydroepiandrosterone, androstenedione and finally to estradiol was documented, providing a hypothetical pathway for steroid metabolism in human breast cancer. The conversion of pregnenolone to 17-hydroxypregnenolone was significantly less in receptor rich tumors and was totally absent in 4 receptor rich tumors with estrogen receptors of over 45 fmol/mg protein.
Steroids 1979 Dec
PMID:Metabolism of pregnenolone by human breast cancer. Evidence for 17 alpha-hydroxylase and 17,20-lyase. 16 34

Studies of the temperature sensitivity of estradiol receptor binding in rabbit uterine cytosol have revealed the existence of an enzyme which catalyzes the covalent binding of estradiol to cytosol proteins. A fraction, prepared by chromatography on Biogel P-200 and incubated at 37 degrees C in the presence of Mn++, exhibited a time-dependent, temperature-sensitive, oxidative binding of estradiol not seen in the crude cytosol preparation. Although the activity of this enzyme was shown to be independent of estradiol binding by the high affinity estrogen receptor, its presence may complicate studies of estrogen receptor action which involve the use of elevated temperatures.
Steroids 1975 Jan
PMID:A manganese catalyzed covalent binding of estradiol - 17 beta to cytosol proteins of rabbit uterus. 16 43

The effect of androgens on the nuclear uptake of both tritiated estradiol (3H-E2) and the estrogen receptor was studied in immature rat uteri. It was demonstrated that in vitro preincubation of immature rat uteri with various androgens (1 muM to 50 muM) followed by incubation with 3H-E2 (20 nM) resulted in a greatly decreased specific nuclear uptake of 3H-E2. Non-androgenic steroids had no effect. It was also confirmed that 5alpha-dihydrotestosterone (DHT) causes the accumulation of the estrogen receptor in the nuclei of uterine tissue. In vitro incubations of rat uteri with DHT (1muM and 50muM) were found to cause maximal nuclear estrogen receptor accumulation to the same degree as caused by estradiol, i.e. the nuclear uptake of approximately 100% of the estrogen receptor. Antiandrogens, which block the binding of androgens to the testosterone receptor in various tissues, did not inhibit the DHT - induced decrease in the 3H-E2 uptake by the uterine nuclei or the DHT - caused accumulation of the estrogen receptor in nuclei. These results seem to indicate that the uterine testosterone receptor has no role in the androgen - induced nuclear uptake of the estrogen receptor. However, the non-steroidal antiestrogens inhibited the DHT - induced nuclear accumulation of the estrogen receptor. This would seem to indicate that the estrogen - and androgen - induced nuclear accumulation of the estrogen receptor share a common mechanism.
Steroids 1975 Feb
PMID:Androgen-induced nuclear accumulation of the estrogen receptor. 16 64

Estrogen receptor is shown to be present in the livers of adult rats. The receptor binds estradiol-17beta with a Kd of 1 x 10(-10) M and sediments at 8 S in sucrose gradients. Other estrogens and anti-estrogens compete for estradiol binding, while nonestrogenic steroids do not. Receptor levels fall dramatically after hypophysectomy, but can be partially restored within 18 hours by a single injection of prolactin. It is known that prolactin critically regulates the level of its own receptor in the liver, and we now suggest that it also exerts a primary control over the availability of liver estrogen receptor.
Steroids 1975 Sep
PMID:Estrogen receptor in rat liver and its dependence on prolactin. 17 45

The metabolism of 7alpha-3H-dehydroepiandrosterone was studied in six human breast carcinomas in vitro. All mammary tumors transformed DHA to testosterone, dihydrotestosterone, 5alpha-androstane-3alpha, 17beta-diol and 5alpha-androstane-3,17-dione. Of the tumors investigated, three estrogen receptor-negative tumors converted DHA to estradiol and only one estrogen receptor-positive tumor produced estradiol from DHA. Observations on the relationship of androgen metabolism and hormone dependency are discussed.
Steroids 1975 Oct
PMID:Metabolism of dehydroepiandrosterone by hormone dependent and hormone independent human breast carcinoma. 17 46

We have identified receptors for glucocorticoids, progestins, and androgens in a human breast tumor cell line (MCF-7) known to have estrogen receptor. Sucrose density gradients show that MCF-7 cytosol contains approximately 100 fm/mg protein estradiol (E2-3H) receptor, more than 300 fm/mg protein progesterone receptor (measured with R5020-3H), about 40 fm/mg protein 5alpha-dihydrotestosterone (5alpha-DHT-3H) receptor, and 800 fm/mg glucocorticoid receptor (measured with dexamethasone-3H). Dissociation constants obtained by Scatchard analyses were approximately 0.6 x 10(-10)M (E2), 1 x 10(-9)M (R5020), 2.8 x 10(-10)M (5alpha-DHT) and 8 x 10(-9)M (dexamethasone). No cross competition was found for estrogen receptor, but progestins competed for androgen and glucocorticoid binding. The androgen, but not the glucocorticoid, partially competed for R5020 binding to progesterone receptor. This first demonstration of 4 classes of steroid receptors in human breast cancer means that MCF-7 may be an excellent in vitro model for studying the mechanism of tumor response to endocrine therapy as well as the complex relationships between binding and biological actions of these hormones.
Steroids 1975 Dec
PMID:MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. 17 27

The relationship between the quantity of nuclear estrogen receptor complex formed and the amount of peroxidase induced by estradiol in immature rat uteri was determined. A good correlation was obtained between the quantity of 3H-estradiol specifically bound to the nuclear pellet and the amount of enzyme present 12 h after treatment with physiological doses of estrogen. Nafoxidine (U-11,100A) administered together with estrogen reduced signficantly the increase in peroxidase activity brought about by estradiol. Pretreatment with nafoxidine was less effective. The possible mechanism of action of this antiestrogen is discussed.
Steroids 1976 May
PMID:Effect of nafoxidine (U-11,100A) on the induction of uterine peroxidase. 18 72


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