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

The effects of estradiol, progesterone, and tamoxifen on the activity of estradiol 2- and 16 alpha-hydroxylases were studied in human breast cancer cell cultures using a radiometric assay. After 5 days' exposure to these compounds, incubations in the presence of either [2-3H]estradiol or [16 alpha-3H]estradiol as substrate were carried out. In MCF-7 cells, estradiol (10(-8) M), progesterone (10(-6) M) and tamoxifen (10(-6) M) significantly increased 16 alpha-hydroxylase activity (estradiol; 21% progesterone 10% to 32%; tamoxifen 21% to 31%; P less than 0.01). Synergistic effects were observed when the cells were successively exposed to tamoxifen and progesterone. Simultaneous treatment with tamoxifen plus estradiol or estradiol plus progesterone showed no change from estradiol alone. On the other hand, although estradiol had no direct effects on 2-hydroxylase activity, tamoxifen decreased this enzymatic activity significantly at 10(-6) M (23% to 37%). Progesterone acted synergistically to further decrease this reaction. Treatment with only progesterone caused an increase in 2-hydroxylation. In contrast, a subline of MCF-7 cells with low estrogen receptor levels showed only minimal enzyme-hormone responses. Likewise, treatment of the estrogen receptor-negative MDA-MB-231 human breast cancer cell line with these compounds showed no effects on either 2- or 16 alpha-hydroxylase activity. In the progesterone receptor-rich T47D cell line, estradiol decreased both activities while progesterone increased both.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1990 Jul
PMID:Induction and inhibition of estradiol hydroxylase activities in MCF-7 human breast cancer cells in culture. 221 96

Progesterone was transformed microbiologically by the fungal strain Curvularia clavata Jain. Progesterone (I) was added as substrate when the microorganism reached its exponential growth phase. Three substances were isolated after the fermentation: a non-steroidal substance, radicinin (II), which has been established to be a metabolic product of the fungus and acts as a phytotoxin, and two steroidal substances which resulted from fungal enzymatic action on the progesterone molecule. The structure of each microbial metabolite was elucidated by 1H-nuclear magnetic resonance, mass spectrometry, and infrared and UV analyses, and the yields were determined by high-pressure liquid chromatography. The progesterone metabolites were characterized as 7 alpha,14 alpha-dihydroxypregn-4-ene-3,20-dione (III) and 11 beta, 14 alpha-dihydroxypregn-4-ene-3,20-dione (IV). Evidence for the structure of these steroidal products came from derivatives resulting from acetylation and dehydration.
Steroids 1990 Jan
PMID:Microbiologic transformation of progesterone by Curvularia clavata Jain. 230 53

Uteri and cervices were obtained from estrous rabbits (controls) and from rabbits 24 h or 7 days after a single intramuscular injection of medroxyprogesterone acetate (MPA; 2.14 mg/kg). Estrogen and progesterone receptor concentrations were measured by Scatchard analysis, cell-free DNA synthesis was measured by (3H)-TTP incorporation, and tissue sections were examined histologically. The uterine endometrium underwent marked changes in histology, including extensive infoldings of the mucosal surface, glands were continuous into crypts and secretory epithelial cells were noted. In addition, total estrogen receptor content and DNA synthesis were decreased. In contrast, there was no significant change in the histology of the endocervical epithelial-stromal complex, and total estrogen receptor remained constant. However, DNA synthesis in the endocervix was decreased. Thus we conclude that: DNA synthesis is not linked to changes in estrogen receptor in the endocervix; and differential effects of progestogen on the estrogen receptor system occur coincident with different morphological responses within two target tissues from the same animal.
Steroids
PMID:Differential responses of rabbit endocervix and uterus to medroxyprogesterone acetate. 294 53

Preeclampsia is characterized by imbalances in the production rates of several arachidonic acid metabolites. There is a considerable amount of evidence to indicate that PGI2 production is decreased in preeclampsia. PGI2 is a potent vasodilator, an inhibitor of platelet aggregation, and an inhibitor of uterine contractility. Evidence is accumulating that TX production in preeclampsia is either increased or unchanged so that the ratio of TX to PGI2 favors TX. TX opposes the actions of PGI2 in that it is a potent vasoconstrictor, a stimulator of platelet aggregation, and a stimulator of uterine contractility. Therefore, an imbalance of increased TX/decreased PGI2 production can account for the major clinical symptoms of preeclampsia. There is now preliminary evidence that the placenta produces lipoxygenase, as well as cyclooxygenase compounds. The hydroxyeicosatetranoic acids (5-HETE, 12-HETE, 15-HETE) and LTB4 have been identified as placental products. The preeclamptic placenta appears to be deficient in the 5- and 12-lipoxygenase enzymes, as indicated by placental production of 5-HETE and 12-HETE. Little is known about the regulation of arachidonic acid metabolites in normal or preeclamptic pregnancies. Steroids are known to affect cyclooxygenase product production. Progesterone, for example, inhibits PGI2 production. Although circulating and urinary concentrations of progesterone do not differ between normal and preeclamptic pregnancies, there is one report that placental progesterone concentrations are higher in preeclampsia; this may partially explain the decreased placental production of PGI2. There is a considerable amount of evidence in various tissues that regulatory interactions exist between the cyclooxygenase and lipoxygenase metabolites of arachidonic acid, but the role of these interactions in preeclampsia is not known. There is still much to be learned about the etiology of preeclampsia, but it is certain that aberrations in the production of arachidonic acid metabolites play an important role. It is likely that the effective treatment of preeclampsia will come from understanding the regulation of the arachidonic acid metabolites during pregnancy, and, therefore, the ability to specifically treat the production imbalances that characterize this disorder.
 ...
PMID:The role of arachidonic acid metabolites in preeclampsia. 303 19

[4-14C]Progesterone was administered to two cycling female monkeys during the luteal phase of the cycle, and blood and urine were sampled over a 24 h period. Progesterone had a volume of distribution of 1.75 +/- 0.3 L/kg, and a plasma elimination clearance of 0.06 +/- 0.03 L/kg/min. In comparison to the human, plasma progesterone binding was greater and progesterone clearance was slower in the cynomolgus monkey. The major unconjugated metabolite in plasma was 20 alpha-hydroxy-4-pregnen-3-one. In urine 6.2% of 14C-steroids were unconjugated, 2.3% of which were [14C]progesterone. Thin-layer chromatography (TLC) of conjugated metabolites in urine revealed that 24% had the mobility of sulfates, 19% that of glucuronides, and 52% were more polar. After hydrolysis of conjugates, a major fraction chromatographed with pregnanediol. However, despite evidence for the presence of a 20 alpha-hydroxyl group, none of the pregnanediol isomers could be identified among these 14C-steroids. Nevertheless, over 80% of urinary metabolites had sufficient analogy to pregnanediol to bind to an antiserum specific for ring D and the C-17 side-chain of pregnanediol.
Steroids 1988 Sep
PMID:Metabolism and pharmacokinetics of progesterone in the cynomolgus monkey (Macaca fascicularis). 325 28

The synthetic hapten 11 alpha-hemisuccinylprogesterone (11 alpha-hemisuccinyl-pregn-4-ene-3,20-dione), when linked to the appropriate macromolecular carrier, has been used successfully as a solid-phase antigen for progesterone detection in immunoassay. In this study the synthesis of 11 alpha-hemisuccinylprogesterone from 11 alpha-hydroxyprogesterone has been improved by using 4-dimethylaminopyridine (DMAP in refluxing dioxane, a highly nucleophilic polar solvent.
Steroids
PMID:A rapid approach to 11 alpha-hemisuccinylprogesterone synthesis. 325 31

Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta- androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10(-6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action.
Steroids
PMID:Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation. 333 39

Progesterone, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH), 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-DHP), 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol in ovarian venous plasma of androgen-sterilized rats treated with 25 IU of human chorionic gonadotropin (hCG) were assayed by gas chromatography. The compounds listed were essentially undetectable in polycystic ovaries of the androgen-sterilized rats. However, after injection of hCG, levels of these steroids were high. Levels of progesterone and 5 alpha-pregnane compounds reached a peak within 1 or 2 days after hCG treatment and then fell slowly. The level of 20 alpha-DHP reached a peak on day 4 after hCG treatment and remained high thereafter. Injection of 2 micrograms of luteinizing hormone (LH) before sample collection increased the secretion of progesterone at all times tested except when it was already at a peak. The secretion of 5 alpha-DHP and 3 alpha-OH was also increased by LH after hCG treatment, but the ability of the ovary to produce these steroids was not, suggesting that there was low 5 alpha-reductase activity in the cystic ovary before hCG treatment. The results suggest that ovulation and luteinization in cystic follicles may cause the low activities of 5 alpha-reductase and 20 alpha-hydroxysteroid dehydrogenase in polycystic ovaries of androgen-sterilized rats to increase.
Steroids
PMID:Secretion of pregnane compounds from polycystic ovaries of androgen-sterilized rats. 344 81

Tritiated [(16 alpha-ethyl-21-hydroxy-19-nor-pregn-4-ene-3,20-dione)-6,7-3H] (ORG-2058) and 17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020) were compared as ligands in the assay of progesterone receptor in human and rat breast tumors. We found that ORG-2058 is a better ligand because of its low nonspecific binding. Most of the nonspecific binding of the other ligand R5020, is to proteins which bind corticosteroids. In cancerous tissue ORG-2058 binds to progesterone receptor linearly in a range of protein concentrations which are normally used in the receptor assay. On the other hand, R5020 exhibits binding linearity over a narrower protein concentration in many tumor biopsies, which may cause severe limitation in the assay procedure or frequent underestimation of receptor content.
Steroids
PMID:ORG-2058 as a ligand in the assay of progesterone receptor in breast cancer. 344 91

Progesterone, 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH), 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-DHP), 20 alpha-hydroxy-5 alpha-pregnan-3-one (20 alpha, 5 alpha), and 5 alpha-pregnane-3 alpha, 20 alpha-diol (DIOL) in ovarian venous plasma at first ovulation in female rats treated on day 30 with 10 IU of pregnant mare's serum gonadotropin (PMSG) were assayed using gas chromatography. Progesterone peaked at late proestrus before ovulation (day 32) and at early diestrus after ovulation (day 34). With the first peak, 5 alpha-DHP and 3 alpha-OH increased. The 20 alpha-DHP level peaked at early diestrus after ovulation (day 34) and remained high thereafter. The 20 alpha, 5 alpha and DIOL peaked at estrus after ovulation (day 33) and then fell slowly. Injection of 2 micrograms of luteinizing hormone (LH) before sample collection increased secretion of 20-keto-pregnane compounds, except when they were at peak levels. The secretion of 20 alpha-hydroxy-pregnane compounds was unaffected by LH at all times tested. These results suggest that rat ovaries without corpora lutea secrete 20-keto-pregnane compounds in response to LH, but that 20 alpha-hydroxy-pregnane compounds are secreted only from ovaries with corpora lutea.
Steroids
PMID:Ovarian secretion of pregnane compounds at first ovulation in rats treated with pregnant mare's serum gonadotropin. 359 Feb 43


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