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

A method for separation and analysis of conjugates of ethynylestradiol in urine is described. Steroid conjugates are separated on a lipophilic strong anion exchanger (triethylaminohydroxypropyl Sephadex LH-230), and phenolic steroids released by enzyme hydrolysis or solvolysis ar isolated by chromatography on the same ion exchanger. Steroids carrying an ethynyl group are isolated by chromatography on SP-Sephadex (Ag+). Ethynylestradiol is analyzed by gas chromatography-mass spectrometry of the trimethylsilyl ether, using [9,11,11,12,12-(2)H5] ethynylestradiol and internal standard.
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PMID:Analysis of isomeric ethynylestradiol glucuronides in urine. 732 Jan 16

Types and patterns of radioactive urinary conjugates were examined by Sephadex LH-20 chromatography after ingestion of radiolabeled mestranol and/or ethinyl estradiol in a variety of populations. Women in Nigeria, Sri Lanka, and the United States were given the radioactive estrogens. Over 3 days, no differences in total excretion of urinary radioactivity were found. However, there were consistent geographical differences in the proportion of 3-, 17-, and 3,17-glucuronides, indicating significant geographical differences in hepatic metabolism of ethinyl estrogens. Then high-performance liquid chromatographic patterns of urinary aglycone metabolites of mestranol and ethinyl estradiol were studied after successful separation on a Chromegaprep Diol column. Ethinyl estrogen metabolism showed great individual variation. Ethinyl estradiol was the principal compound excreted after ingesting either ethinyl estradiol or mestranol. Unmetabolized mestranol was found as well. Ethinyl estradiol and mestranol profiles were similar, with ethinyl estradiol demonstrating a more complex pattern. U. S. subjects displayed extensive oxidative metabolism (Positions 2, 6, and 16), Sri Lankans less Nigerians very little if any. No difference in metabolic patterns was seen among long-term vs. short-term users vs. nonusers.
Steroids 1980 Sep
PMID:Chromatographic patterns of urinary ethynyl estrogen metabolites in various populations. 743

Estrogen sulfamates are promising hormones by oral administration. Therefore, generally applicable and convenient methods for the multigram synthesis of these derivatives are desirable. Numerous estra-1,3,5(10)-trienes derived from estrone, estradiol. 14 alpha,15 alpha-methylenestradiol, ethinylestradiol, and estriol have been esterified with sulfamoyl chloride and N-methylsulfamoyl chloride by a novel approach involving the use of 2,6-di-tert-butylpyridines as bases and chemoselective hydroxy group protections. These pathways circumvent the nonselective formation of esters and side reactions by in situ generated azasulfenes. For toxicological and clinical studies a new synthesis of estrone sulfamate on a 100-g scale was developed using dimethylformamide as the solvent and base.
Steroids 1996 Dec
PMID:Synthesis of estrogen sulfamates: compounds with a novel endocrinological profile. 898 40

Estrogen treatment affects the hepatic synthesis and/or secretion of several proteins involved in clinically important pathological processes such as atherosclerosis, hypertension, and thrombosis. The endocrine regulation of the estrogen receptor (ER) concentration in primary cultures of rat hepatocytes was studied. Human growth hormone (hGH) and dexamethasone (DEX) in combination increased ER concentration 6-fold and ER mRNA levels 2.5-fold. These effects were not significantly different from those observed after treatment with the purely somatogenic bovine growth hormone (GH) in combination with DEX. Treatment with the lactogen ovine prolactin in the presence or absence of DEX did not significantly affect ER or ER mRNA concentrations. Triiodothyronine treatment at the most effective concentration (50 nM) increased ER and ER mRNA levels twofold. Medium supplementation with estradiol (0.1 nM) throughout the experiment did not affect the response to treatment with hGH and DEX. Treatment with high concentrations of ethinylestradiol in combination with hGH and DEX, however, increased the ER level twice as much as hGH and DEX without addition of estradiol or ethinylestradiol, whereas the ER mRNA concentration was the same in both the GH+DEX group and GH+ DEX+ (estradiol or ethinylestradiol) groups. These data indicate the importance of GH in combination with glucocorticoids for the maintenance of ER concentrations in the rat liver. Thyroid hormones may be of some, although minor importance, whereas the data suggest that prolactin is not directly involved in hepatic ER regulation.
Steroids 1997 Oct
PMID:Hormonal regulation of the estrogen receptor in primary cultures of hepatocytes from female rats. 938 11

Estrogen is of vital importance for the development and control of reproductive functions. Until recently, estrogen was believed to regulate complex programs of gene expression by binding to an unique nuclear receptor belonging to the superfamily of ligand-dependent transcription factors. However, the identification of a second estrogen receptor, referred to as ER beta, is leading to a re-evaluation of estrogen signaling and physiology.
Steroids
PMID:Estrogen receptor beta: re-evaluation of estrogen and antiestrogen signaling. 961 97

Estrogen levels in breast tumors of post-menopausal women are as much as 10 times higher than estrogen levels in plasma, presumably due to in situ formation of estrogen. The major source of estrogen in breast cancer cells may be conversion of estrone sulfate to estrone by the enzyme estrone sulfatase. Thus, inhibitors of estrone sulfatase have potential for the treatment of estrogen-dependent breast cancers. Several steroidal agents have been developed that are potent estrone sulfatase inhibitors, most notably estrone-3-O-sulfamate. These compounds may have undesired actions, especially estrogenicity. Recently, non-steroidal estrone sulfatase inhibitors have been designed that avoid the problems associated with an active steroid nucleus; however, these have not achieved the potency of estrone-3-O sulfamate. We have designed and synthesized a series of compounds, 17 beta-(N-alkylcarbamoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (6a-d) and 17 beta-(N-alkanoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (11a-d) that combine the structural features of the steroidal estrone sulfatase inhibitors with a membrane insertion region that should increase the affinity for the sulfatase enzyme and decrease the estrogenicity of the steroid. We tested the compounds for estrone sulfatase inhibition by measuring estrone sulfatase activity in intact cultures of human breast cancer cells (MDA-MB-231). We tested for estrogenicity by measuring growth of estrogen-dependent MCF-7 human breast cancer cells. All of the test compounds (10 nM) substantially inhibited estrogen sulfatase activity of intact MDA-MB-231 cells. Dose-response analysis indicated an IC50 of approximately 0.5 nM for two of the compounds (6a and 11a). In the test for estrogenicity, estrone and estrone-3-O-sulfamate significantly stimulated MCF-7 cell growth. In contrast, neither the 17 beta-(N-alkylcarbamoyl)-estra-1,3,5,(10)-trien-3-O-sulfamates++ + nor the 17 beta-(N)-alkanoyl)-estra-1,3,5,(10)-trien-3-O-sulfamates stimulated growth of MCF-7 cells at a concentration of 1 microM, indicating that they are not estrogenic at levels 2000 times greater than their IC50 for estrone sulfatase. Our data indicate the utility of the new compounds for inhibition of breast cancer cell estrone sulfatase activity. Further, our data support the concept that estrone sulfatase inhibitors may be useful as therapeutic agents for estrogen-dependent breast cancers.
Steroids
PMID:Development of potent non-estrogenic estrone sulfatase inhibitors. 965 50

Spawnings of scleractinian corals are affected by light, temperature, and other environmental cues, but no studies elucidate physiological mechanisms that regulate coral gametogenesis. We hypothesized that estrogens may act as bioregulators of coral reproduction. Estrone (E1) and estradiol-17 beta (E2) concentrations were measured in homogenates of tissue and skeleton from M. verrucosa. Tissue samples were collected monthly throughout the year, and more frequently in July and August around spawning. Steroids were extracted with diethyl ether, purified via celite chromatography and assayed with radioimmunoassay. Non-specific binding in coral tissue varied with sample weight and was elevated relative to standards. Monthly mean E1 ranged from 20-70 ng E1 g ash-free dry weight (AFDW)-1, with highest values in April. Smaller asynchronous peaks occurred in early July, prior to spawning. Monthly mean E2 ranged from 8-25 ng E2 g AFDW-1, with highest values in February and March. Peaks in E2 preceded peaks in E1, indicating metabolism of a pool of estrogen. E1 was positively correlated with protein concentration, which is consistent with a bioregulatory role of estrogens. Estrogen peaks in spring and prior to the July spawn corroborate our hypothesis that estrogens regulate coral gametogenesis and spawning.
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PMID:Estrone and estradiol-17 beta concentration in tissue of the scleractinian coral, Montipora verrucosa. 1021 33

Estrogen modulates a variety of functions, most of which can be explained by the classical genomic mechanism of action. However, a number of estrogen's actions appear to be incompatible with this mechanism and fall into the category of nongenomic. In the hippocampus, application of 17beta-estradiol rapidly enhances the amplitude of kainate-induced currents of CA1 neurons. The potentiation resulted from a cyclic adenosine monophosphate-dependent phosphorylation process rather than a direct allosteric modulation of AMPA/kainate receptors. To initiate this potentiation, estrogen is required on both sides of the plasma membrane. Extracellularly, estrogen appears to activate a G-protein-coupled receptor, whereas the intracellular action of estrogen appears to be a modulation of the balance between phosphorylation and dephosphorylation. The binding sites responsible for the potentiation are genetically or pharmacologically distinct from both estrogen receptors alpha and beta. These findings provide support for the concept of a novel mechanism of action for estrogen.
Steroids
PMID:Estrogen: mechanisms for a rapid action in CA1 hippocampal neurons. 1032 68

Estrogen is an important atheroprotective molecule that causes the rapid dilation of blood vessels by stimulating endothelial nitric oxide synthase (eNOS). There is also evidence that estrogen modulates airway epithelial NO production, thereby potentially affecting bronchial hyperresponsiveness. Studies in cultured endothelial and airway epithelial cells indicate that physiologic concentrations of estrogen cause rapid direct activation of eNOS that is unaffected by actinomycin D, but fully inhibited by estrogen receptor (ER) antagonism. Overexpression of ERalpha leads to marked enhancement of the acute response to estrogen, and this process is blocked by ER antagonism, it is specific to estrogen, and it requires the ERalpha hormone binding domain. In addition, the acute response of eNOS to estrogen can be reconstituted in COS-7 cells cotransfected with wild-type ERalpha and eNOS, but not by transfection with eNOS alone. Furthermore, the inhibition of calcium influx, or tyrosine kinases or MAP kinase prevents the stimulation of eNOS by estrogen, and estrogen causes rapid ER-dependent activation of MAP kinase. These findings indicate that the acute effects of estrogen on both endothelial and airway epithelial eNOS are mediated by ERalpha functioning in a novel, nongenomic manner to activate the enzyme via calcium-dependent, MAP kinase-dependent mechanisms.
Steroids
PMID:Rapid activation of endothelial nitric oxide synthase by estrogen. 1032 70

Estrogen replacement therapy (ERT) increases a woman's risk of developing endometrial cancer approximately 120% for each 5 years of use. ERT increases a woman's risk of developing breast cancer approximately 10% for each 5 years of use. To reduce the greatly increased endometrial cancer risk, progestins have been added to ERT (estrogen-progestin replacement therapy; EPRT) for between 5 and 15 days (usually 7 or 10 days) per month in a sequential fashion (sequential EPRT; SEPRT) or with each dose of ERT (continuous-combined EPRT; CEPRT). We conducted two large case-control studies in postmenopausal women in Los Angeles to evaluate the effects of these changes on endometrial and breast cancer risks. As expected CEPRT was not associated with any increased risk of endometrial cancer. SEPRT with the progestin being given for 10 days per month also did not increase endometrial cancer risk. SEPRT with the progestin being given for 7 days per month did increase endometrial cancer risk with only a relatively slight reduction in risk compared to ERT effectively proportional to the reduction in the number of days of unopposed estrogen. The sharp contrast between the effects of 7 days and 10 days of progestin in SEPRT suggests that the extent of endometrial sloughing or of 'terminal' differentiation at the completion of the progestin phase may play a critical role in determining endometrial cancer risk. This may provide an explanation of why endometrial cancer risk increases so sharply with age in young women even in countries where obesity-associated anovulation is very uncommon; extended periods of unopposed estrogen is not an explanation but less than 10 days of an 'adequate' progesterone level may be. EPRT significantly increased the risk of breast cancer. EPRT was associated with an approximately 24% increase in risk for each 5 years of use; the effect was some 212-fold greater than the effect of ERT, which we had previously predicted on theoretical grounds. This effect could also be predicted from the results on mammographic densities seen in the PEPI randomized trial of different forms of hormone replacement therapy (HRT). In the PEPI trial EPRT increased mammographic densities to a much greater extent than ERT. Progestins need to be given to protect the endometrium. They need to be delivered to the endometrium in a manner that will have the least effect on the breast. This can be carried out by using a vaginal or direct endometrial route of administration. The vaginal route will provide adequate endometrial progestin levels with low blood levels so that the effects of the progestin on the breast should be small; with the direct endometrial route the blood progestin levels are even lower, and the effects of the progestin on the breast will be effectively zero. If this is unacceptable to a woman, then giving progestins by mouth (or transdermally) for 10 days every 3 to 4 months should provide satisfactory protection of the endometrium when used with standard-dose conjugated estrogen (CE). This regimen has much less effect on the breast than monthly SEPRT or CEPRT. Two clinical trials of 10 mg per day of MPA for 14 days every 3 months and 0.625 mg/day of CE have been published. Both studies suggest that this approach may be satisfactory in that the extent of hyperplasia was minimal. More studies of this approach are urgently needed.
Steroids
PMID:Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer. 1110 73


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