Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubations of tritiated 17alpha-ethynylestradiol (EE2) with liver explants of baboon and mouse showed the primate species to be more efficient in the removal of the ethynyl group. Liver microsomes from sexually immature male and female baboons were then incubated with tritiated EE2 and estradiol (E2). Each hormone bound irreversibly to the microsomal pellet. Addition of glutathione reduced the irreversible or covalent association. Incubations with E2 demonstrated significant conversion to estrone (E1). The EE2 experiments demonstrated a conversion to estrone only in the presence of an NADPH-generating system, and the addition of SKF-525A reduced the conversion of EE2 to E1. The cleavage reaction appears to be an oxidative event.
Steroids 1977 Jul
PMID:Oxidative metabolism and de-ethynylation of 17alpha-ethynylestradiol by baboon liver microsomes. 2 74

This study has characterized two new enzymatic hydroxylase activities specific for 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) in the rat ventral prostate: 5 alpha-androstane-3 beta, 17 beta-diol 6 alpha-hydroxylase (6 alpha-hydroxylase) and 5 alpha-androstane-3 beta, 17 beta-diol 7 alpha-hydroxylase (7 alpha-hydroxylase). Both of these irreversible hydroxylase activities require NADPH and are localized in the microsomal fraction of the prostate. The apparent Km for 3 beta-diol is 2.5 microM for both the 6 alpha- and 7 alpha-hydroxylase activities. The apparent Km for NADPH is 7.6 microM for the 6 alpha-hydroxylase and 7.0 microM for the 7 alpha-hydroxylase. The pH optimum for both activities is 7.4. Several steroid inhibitors of these hydroxylase activities in vitro were identified including cholesterol, progesterone, and estradiol. Estradiol was found in vitro to be a noncompetitive inhibitor (Ki = 5 microM). Injection of estradiol into intact male rats, simultaneously receiving exogenous testosterone, also produced a significant lowering of the 6 alpha-plus 7 alpha-hydroxylase activities. Both the 6 alpha- and 7 alpha-hydroxylase were found to be androgen sensitive. Following castration there is a rapid decrease in both activities.
Steroids 1979 Jun
PMID:Characterization of two new enzymatic activities of the rat ventral prostate: 5 alpha-androstane-3 beta, 17 beta-diol 6 alpha-hydroxylase and 5 alpha-androstane-3 beta, 17 beta-diol 7 alpha-hydroxylase. 3 13

Studies were conducted to further examine the mechanisms responsible for gonadal hormone effects on the rat adrenocortical 11beta-hydroxylase system. Despite higher concentrations of cytochrome P-450 and larger 11-deoxycorticosterone (DOC)-induced difference spectra in adrenal mitochondria from females than males, no sex difference in 11beta-hydroxylase activity was observed. The pregnenolone-induced difference spectrum, indicative of cholesterol binding to cytochrome P-450, also was similar in males and females. Testosterone administration to castrated males lowered both 11beta-hydroxylase activity and mitochondrial cytochrome P-450 content. Estradiol produced the opposite effects in castrated females. However, when given to ACTH-replaced hypophysectomized rats, neither testosterone nor estradiol affected cytochrome P-450 levels or the rate of 11beta-hydroxylation. These observations, taken with the known effects of estradiol and testosterone on ACTH secretion in rats and the effects of ACTH on 11beta-hydroxylation, indicate that gonadal hormone effects on the 11beta-hydroxylase system are mediated by ACTH.
Steroids 1975 Jun
PMID:Relation of the pituitary gland to gonadal hormone effects on the adrenocortical 11beta-hydroxylase system in rats. 16 71

Estradiol-binding macromolecules in fetoneonatal rat brain cytosol and serum were compared by immunochemical techniques. When treated by a double diffusion procedure, both cytosol and serum formed precipitin lines with rabbit antiserum specific for perinatal rat serum proteins. These lines fused completely, indicating, within the limits of detection of this particular antiserum, the presence of identical antigenic determinants in the brain and serum. Prior removal of immunoprecipitable material from cytosol or serum, after incubation with the specific antiserum, prevented formation of such precipitin lines. The procedure similarly presented specific estradiol-binding to macromolecules. It was therefore concluded that the specifically perinatal, antigenically similar, components in rat brain cytosol and serum (possibly representing alphafetoprotein) are responsible for the estradiol-binding activity in these two tissue compartments. Measurements of heme concentrations indicated that the alphafetoprotein-like material in the cytosol does not reflect blood contamination, but rather a separate population of similar or identical molecules.
Steroids 1975 Aug
PMID:Immunochemical comparison of estradiol-binding molecules in perinatal rat brain cytosol and serum. 17 7

The present study was done to determine if a progesterone receptor is present in rat pituitary. Cytosol was labeled with 3H-progesterone (3HP) or 3H-R5020 (3HR) and subjected to sucrose-glycerol density-gradient centrifugation. Serum progesterone was measured for correlation with progesterone receptor levels. Two 3HP-binding peaks (4S + 6S) were evident in uterine and pituitary cytosols. The 4S peak was eliminated by competition with unlabeled cortisol leaving a single 6S peak (progesterone receptor). Estradiol (E) priming of the male or female rat increased progesterone receptor levels in pituitary cytosol as demonstrated using 3HP and 3HR, and pituitary progesterone receptor bound 3HR with a higher affinity than 3HP. Following adrenalectomy of gonadectomized rats, progesterone receptor levels were increased in pituitary and uterine cytosol of both E-primed and unprimed groups. An inverse relationship was established between serum progesterone and progesterone receptor levels in the uterus and pituitary suggesting that stress-induced adrenal progesterone secretion significantly influences progesterone receptor levels in the rat. These results demonstrate an estrogen-inducible progesterone receptor in the rat pituitary with properties similar to those of the uterine progesterone receptor.
Steroids 1978 Jan
PMID:Progesterone receptor in the rat anterior pituitary: effect of estrogen priming and adrenalectomy. 66 58

Incubation parameters for a radioderivative assay for estrogen 2-hydroxylase have been examined. The assay was found to be specific and sensitive if a chromatographically purified preparation of COMT was used. Estradiol was found to be a better substrate for the 2-hydroxylase than estrone or estriol. The liver had significantly higher estrogen 2-hydroxylase activity than any other tissue examined. The estrogen 2-hydroxylase was highly localized in the microsomal fraction in both the liver and the brain. The male rat was found to have significantly more estrogen 2-hydroxylase activity in the liver than the female rat. In addition, in the male rat liver, the estrogen 2-hydroxylase activity was reversibly inducible by testosterone and was not affected by phenobarbital. In the male and female rat brain the estrogen 2-hydroxylase activities were similar.
Steroids 1978 Nov
PMID:Estrogen 2-hydroxylase: activity in rat tissues. 72 79

Estradiol binding components in the cytosol and nuclear fractions of the ovary from immature rats (22-28 days old) were characterized by in vitro methods. Several of the biochemical characteristics of the estradiol binding components in the ovarian tissue were compared with the estradiol receptor from the uterus. The results suggest that the ovarian estradiol binding components are similar to the specific high affinity estradiol receptors in the uterus. In the cytosol of intact rat ovary a significant fraction of the total binding sites was found to be occupied, presumably by the endogenous estrogen. Following hypophysectomy there was a significant increase in the available cytosol binding sites. Evidence for translocation of cytosol receptor-estrogen (RE) complex to the nucleus was obtained for the ovary. The sedimentation properties of the RE complex of the ovary and the uterus are similar. The ovarian cytosol RE complex sediments at 7-8S in glycerol gradients at low ionic strength and at 4S in sucrose gradients at high ionic strength. Following extraction with 0.4 M KCl the ovarain nuclear RE complex sediments at 5S in sucrose gradients which is identical to that of the uterine nuclear receptor.
Steroids 1977 Feb
PMID:Estradiol-17beta receptors in the immature rat ovary. 84 22

Adult female rats were given daily subcutaneous injections of 17beta-estradiol-3-benzoate, 25 mug/day for twenty days. Rats were then killed under four different experimental conditions: (1) Fasting, killed in the morning (FM), (2) Non-fasting, killed in the morning (NFM), (3) Fasting, killed at night (FN), and (4) Non-fasting, killed at night (NFN). Estradiol induced a three-fold increase in hepatic cholesterol 7alpha-hydroxylase activity in group FM and a significant increase in group NFN. Although increases in 7alhpa-hydroxylase activity might be associated with lower serum cholesterol levels (by increasing the rate of conversion of cholesterol to bile acids), serum cholesterol concentrations were, in fact, elevated in all rats given estradiol.
Steroids 1977 Feb
PMID:Stimulation of hepatic cholesterol 7alpha-hydroxylase activity by administration of an estrogen (17beta-estradiol-3-benzoate) to female rats. 84 23

Urinary and liver conjugates and 17alpha-ethinyl estradiol (EE2) were chromatographically characterized in normal and castrate women. 5 distinct peaks were found in samples from women receiving EE2, with considerable variations between individuals. The dominant conjugate types excreted were glucosiduronate fractions. 5 conjugate types were also observed during in vitro incubation of normal human liver. Concomitant intravenous administration of carbon-14-EE2 and oral administration of tritiated-EE2 resulted in the conversion to identical conjugates and free steroid products, with carbon-14-EE2 being excreted in greater amounts. The 3-glucuronide of EE2 was synthesized and its relation to the urinary conjugate peaks was demonstrated.
Steroids 1976 Jun
PMID:Human urinary and liver conjugates of 17alpha-ethnylestradiol. 94 Nov 95

Ten steroids have been compared for their ability to modify the rate of uptake of acridine orange by rat liver and by rat liver lysosomes in vivo. The short-term effects of the ten steroids on the specific activity of a lysosomal enzyme, beta-N-acetylglucosaminidase, were also compared. Five of the ten steroids were administered as tritium-labelled compounds and the concentration of steroids or metabolites was measured in rat liver and liver lysosomes at 2.5h and 3.75h after administration. Cortisone acetate, etiocholanolone (5-beta-androstan-3-alpha-01-17-one) and testosterone accelerate and increase the uptake of acridine orange by rat liver lysosomes. Deoxycorticosterone, corticosterone, triamcinolone (9-alpha-fluoro-11-beta, 17, 21-trihydroxy-16-alpha-methyl-pregna-1, 4-diene-3, 20-dione), estradiol-17-beta and progesterone appear to inhibit the uptake of acridine orange by rat liver lysosomes at 2.5 hours. Cortisol and dexamethasone (9-alpha-fluoro-11-beta, 17, 21-trihydroxy-16-alpha-methyl-pregna-1, 4-diene-3, 20-dione) had little effect. All steroids with the exception of etiocholanolone and deoxycorticosterone increase with the specific activity of beta-N-acetylglucosaminidase in the lysosomal fraction at 2.5h. None of the effects at 2.5h are due to lowered protein levels. Lysosomal concentrations of radioactivity following the administration of tritiated steroids were greated for the glucocorticoids, corticosterone and cortisol. Estradiol-17-beta, progesterone and testosterone showed much lower concentrations of radioactivity in isolated lysosomes. Most of the lysosomal radioactivity (73-96%) was associated with the soluble fraction of the disrupted lysosomes.
Steroids 1975 Mar
PMID:Effects of ten steroids on acridine orange uptake and beta-N-acetylglucosaminidase levels in rat liver lysosomes. 114 79


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