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

The metabolism of dehydroepiandrosterone and testosterone by human mammary tumor was investigated. Estrogen synthesis from dehydroepiandrosterone was observed in 9 of 10 estrogen-receptor-negative tumors and only in 2 of 8 receptor-positive tumors (p less than 0.025). Conversion of testosterone to estrogens was observed in 7 of 8 receptor-negative and 2 of 7 receptor-positive tumors. Tumors which are capable of transforming dehydroepiandrosterone to estrogens were also able to aromatize testosterone suggesting that the presence of the aromatase enzyme is inherent to certain tumor cells. No estrogen formation was detected by the mitochondrial-microsomal fraction of normal breast cells while fractions from both fat cell and tumor cell showed estrogen synthesis. Estrogen formation by tumor cell fraction ranged from 5 to 190 times that observed for fat cells. The physiological significance of these results in the neoplastic tissue and its relationship to hormone dependence are discussed.
Steroids 1979 Feb
PMID:Aromatization of androgens by human breast cancer. 15 71

The effect of estrogen pretreatment was stud-ed on the in vitro metabolism and binding of progesterone in uteri of ovariectomized rats in order to prove the dependence of the metabolism of progesterone on its binding. For this purpose, the extent of progesterone binding was varied in uterine tissue by different estrogen treatment of the rats and compared with the metabolism under the same conditions. The protein content determined in 100 mg tissue was used as parameter indicating the success of the pretreatment. Estrogen exposure of the rats for 30 or 45 hrs. caused a rise of protein amount in uterine tissue which was accompanied by an increase of binding sites of progesterone binding components. The binding sites were determined by charcoal adsorption technique and SCATCHARD-analysis. Under nearly the same success of estrogen pretreatment, the increase of the portein amount and with it the rise of binding sites reduced the amount of progesterone metabolites in uterine tissue. The metabolites were determined by quantitative TLC-analysis of the recovered compounds from uterine segments after incubation with radioactive progesterone. Additionally, an enlarged metabolic rate could be observed after saturation of binding components. It is concluded from the results of these experiments that progesterone binding components are factors limiting the enzymatic conversion of progesterone in rat uterus.
Steroids 1978 Feb
PMID:Progesterone in the uterus. X. Dependence of the in vitro progesterone metabolism on progesterone binding in rat uterus. 56 78

Initial excretion studies with orally administered [monoethyl-1-3H] DES demonstrated the feces to be the principal mode of elimination of DES in the C3H mouse. Metabolic studies with tritiated DES and/or [UL-14C] DES were performed with orally dosed C3H high (MTV+) and low (MTV-) titer MMTV female mice. Extraction and partitioning of the fecal radioactivity demonstrated 77 to 86% (n = 4) to be benzene soluble and the remainder H2O soluble. The principal product in the organic phase following Sephadex LH-20 and HPLC purification was DES. The aqueous phase was resolved by LH-20 into two conjugate fractions that were partially hydrolyzed by beta-glucuronidase. The principal aglycone was chromatographically identical with authentic DES. The urinary conjugates were resolved into six fractions. The four major fractions were 80% hydrolyzable with beta-glucuronidase. Two of these fractions had trans-DES as the principal aglycone, whereas the other two had a major peak similar to but not chromatographically coincident with cis-DES. In certain experiments mice were sequentially dosed with tritium (24 hr) followed by a 14C dose (24 hr). Two mice (MTV+) were also previously fed 1000 ppb DES prior to these experiments. The tritated and 14C products were combined and analyzed simultaneously. This experiment did not reveal significant differences in the metabolism due to the modes of radioactive labeling, MMTV titer, or the prior feeding of DES. The developed methodology was judged to purify quantitatively 90% or more of the DES radioactive products.
Steroids 1978 Apr
PMID:Metabolism of diethylstilbestrol in the C3H mouse: chromatographic systems for the quantitative analysis of DES metabolic products. 66 80

Isolated granulosa cells and theca from proestrous hamsters alone and in recombination, were cultured in order to study steroidogenic capacity of this tissue. Cells from medium size antral follicles (100-300 mum diam.) and large preovulatory follicles (500 plus mum diam.) were used. Steroids were measured by radioimmunoassay. Cultures of cells derived from both sizes of follicles made significant amounts of progesterone for up to 6 days in tissue culture. The preparations from the medium sized antral follicles synthesized little or no estrogen. Of the cells harvested from the preovulatory follicles, the granulosa and theca made moderate amounts of estradiol-17beta while the recombined system made similar to 5 times the estradiol-17beta made by theca or granulosa alone. The results indicate that in the in vitro system used: 1) The hamster follicle cells are similar to other species in that they spontaneously luteinize in culture and secrete large amounts of progesterone, 2) Androgen accumulation is greatest in media from cultured theca of preovulatory follicle, 3) A synergism between theca and granulosa of the large preovulatory follicle exists to effect maximal estrogen synthesis, and 4) Estrogen synthesis is short-lived in vitro in contrast to continued progesterone production.
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PMID:Progesterone, androstenedione, testosterone, estrone, and estradiol synthesis in hamster ovarian follicle cells. 111 80

Estrogen metabolism was studied in spontaneous hyperthyroidism (Graves disease) and in alcoholic cirrhosis of the liver. The plasma concentration of estradiol-17beta (PCE2) was increased in men with hyperthyroidism. Although the metabolic clearance rate of estradiol-17beta (MCRE2) was reduced, the production rate (PR) of the steroid was increased above normal. The MCRE2 was also decreased in women with hyperthyroidism but the PCE2 and PRE2 was unchanged from normal. The conversion ratio of estradiol-17beta (CRE2E1) was increased in both hyperthyroid men and women. The PCE2 was significantly increased in men with cirrhosis of the liver. The MCRE2 was normal and this resulted in an increase in the PRE2 in this disorder. The CRE2E1 was significantly higher than normal. The plasma concentration of estrone (E1) was elevated in men with both disorders.
Steroids 1975 Jul
PMID:Estrogen metabolism in hyperthyroidism and in cirrhosis of the liver. 116 83

Ovarian steroids are associated with the proliferation of normal as well as tumorigenically transformed mammary epithelial cells. The experiments performed in this study were designed to establish that (1) tumorigenic transformation induced by the ras oncogene is associated with alterations in estradiol biotransformation, (2) altered endocrine responsiveness persists in the fully transformed tumor cell phenotype and (3) specific perturbations induced by the ras oncogene can be experimentally downregulated. The ras transfectant pH06T and the tumor-derived T1/Pr1 cells exhibited 3- and 43-fold increases, respectively, in C-16 alpha hydroxylation of estradiol relative to the parental mouse mammary epithelial cells (P less than 0.0001). At the cellular level, this alteration corresponded with approximately 90-fold increase in the anchorage-independent growth of T1/Pr1 cells (P less than 0.0001). Estrogen responsiveness of T1/Pr1 cells was demonstrated by their suppression of growth in phenol red-free and/or tamoxifen-supplemented medium and by the reversal of antiproliferative effect of tamoxifen by phenol red and estradiol. Indole-3-carbinol, a naturally occurring tumor suppressive agent, was able to upregulate C-2 hydroxylation at the expense of C-16 alpha hydroxylation of estradiol. Treatment of T1/Pr1 cells with indole-3-carbinol resulted in a substantial decrease in anchorage-independent growth.
Steroids 1992 Jun
PMID:Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells. 144 Jun 96

The administration of 5 alpha-dihydrotestosterone (5 alpha-DHT) and dexamethasone has been shown to attenuate estrogen-induced prolactin release in the estrogen-primed rat. Therefore, the effect of these compounds was studied on anterior pituitary and uterine estrogen receptors. Injection of 0.8 mg/kg body weight of 5 alpha-DHT to ovariectomized adult rats treated with 2 micrograms estradiol/d for 4 days resulted in a significant decrease in occupied nuclear estrogen receptors of the anterior pituitary but not the uterus. Estrogen priming was essential for 5 alpha-DHT effect on occupied nuclear anterior pituitary estrogen receptors because this effect did not occur in ovariectomized vehicle-treated control animals. The administration of 1 mg/kg body weight of dexamethasone brought about a decrease in uterine but not anterior pituitary nuclear estradiol receptors. These results provide further evidence that the regulation of estrogen receptor dynamics is different in the anterior pituitary and the uterus and that different steroids can exert tissue-specific effects.
Steroids 1992 Jan
PMID:Effect of 5 alpha-dihydrotestosterone and dexamethasone on estrogen receptors of the anterior pituitary and uterus. 158 89

We have previously shown that the intracellular content of c-fos mRNA is rapidly induced (within 1 to 3 hours) in ovariectomized rat or mouse uteri following administration of estradiol. This induction is sensitive to actinomycin D but not to protein synthesis inhibitor puromycin, indicating an effect of estradiol at the transcriptional level, possibly mediated by the estrogen receptor. We have used transient transfection assays with defined regions of the mouse c-fos gene ligated to a reporter plasmid expressing chloramphenicol acetyl transferase to study regulation of this gene by estrogens. These recombinants were transfected in two different estrogen-responsive cell lines, GH4 and MCF-7, and stimulated with estradiol. A two- to five-fold induction of chloramphenicol acetyl transferase activity was observed with a construct containing the intact c-fos promoter and 351 bases of 5'-flanking sequence (-351/+44). A similar induction by estrogen is observed with the endogenous c-fos gene in the two cell lines as determined by RNA blot analysis. Estrogen induction is lost when a construct containing -135/+44 region of the c-fos gene is transfected. Plasmid containing the consensus estrogen response element GGTCAnnnTGACC derived from vitellogenin gene is induced 10- to 50-fold in both estrogen-responsive cell lines. Under identical conditions, the oligonucleotide containing the perfect palindrome GGTCTnnnAGACC, present around the -209 region of the c-fos gene, is completely silent when transfected under the control of thymidine kinase promoter. Additional transfection analysis with a number of c-fos promoter constructs has narrowed the estrogen response region to within the -278 to -135 region upstream of the c-fos promoter.
Steroids 1991 Oct
PMID:Presence of an estradiol response region in the mouse c-fos oncogene. 180 51

Estrogen stimulation of the uterus produces a spectrum of biochemical responses that are customarily linked together. This report is an overview of a series of studies by our laboratory investigating the role of different ligand structures in eliciting hormonal responses. Diethylstilbestrol (DES) and certain structural analogs, indenestrol A (IA), indenestrol B (IB), and pseudo-DES, were used as probes to segregate various genomic responses previously considered interrelated, most notably the events of specific protein synthesis and DNA synthesis. These compounds have weak uterotrophic activity; however, they interact with high affinity specifically with mouse uterine estrogen receptors (ERs). All of them produce stoichiometrically similar amounts of ER complex in the nucleus. Indenestrol A and IB possess a single chiral carbon atom and exist as a mixture of enantiomers (ENTs). Competitive binding assays of pure ENTs and cytosolic ERs demonstrated a stereochemical chiral preference for the IA isomer but not IB. This preference was also evident from nuclear ER occupancy experiments. Biologic activity of the IA ENTs also demonstrated differences as seen by receptor binding. Ornithine decarboxylase (ODC) activity was stimulated 600% by DES and partially by IA (rac). All of the ODC activity produced by IA (rac) was due to the IA(C3)-S ENT. Uterine DNA synthesis was measured after treatment with the IA compounds. Indenestrol A (rac) increased DNA synthesis to 40% of the level seen with DES. The weak ENTs showed no activity and the active ENTs were weaker than the IA racemic. These compounds should be useful probes for studying the individual responses involved in estrogen-induced uterine growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1991 May
PMID:Estrogen receptor stereochemistry: ligand binding and hormonal responsiveness. 187 66

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


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