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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

Hysterectomized women were administered tritiated-17alpha-ethinyl estradiol either iv or orally and their urine collected and assayed for labeled-metabolites. Over 95% of the recovered activity was found as conjugated steroids. These were separated into 4 groups by Sephadex LH-20 chromatography with chloroform-methanol and .01M NaCl. 2 of the groups were almost entirely glucosiduronates. 17alpha-ethinyl estradiol itself was the major component in 3 of the fractions while 2-methoxy-17alpha-ethinyl estradiol was the major component of the 4th. Hydrolysis, chromatography with benzene-methanol, and further purification of each of the 4 fractions yielded similar metabolite patterns. Of the major compounds identified, 5 were ethinyl compounds: 17alpha-ethinyl estradiol, 2-methoxy-17alpha-ethinyl estradiol, 16 beta-hydroxy-17alpha-ethinyl estradiol, 2-hydroxy-17alpha-ethinyl estradiol, and 6 alpha-hydroxy-17alpha-eithinylestradiol; 4 were deethinylated estrogens: estrone, estreadiol-17beta, estriol, and 2-methoxy-estradiol-17 beta.
Steroids 1975 Feb
PMID:The urinary metabolites of 17alpha-ethynylestradiol-9alpha,11xi-3H in women. Chromatographic profiling and indentification of ethynyl and non-ethynyl compounds. 16 63

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

1. Reproduction processes are differently regulated in different species. The gestagen/estrogen ratio is of paramount importance for the evaluation of gestagens. Steroids possessing inherent estrogenicity might act as estrogens in, e.g., rodents like rats and mice, but might be active as gestagens in women (e.g. norethinodrel). 2. There is a good and partly significant correlation between the activity of various gestagens in a number of experimental test models and clinical trials. The same is true for the antiovulatory activity of various gestagens in rats and women. Oral rat tests, however, are not relevant. Receptor tests are not at all suitable for dose finding. 3. Erroneously dissociated peripheral and central (inhibition of ovulation) activity of gestagens are found only if different animal species are used (e.g., test on gonadotropin inhibition in rats, gestagen test in rabbits). This is not the case if both kinds of tests are done in one species (e.g., ovulation inhibition test in rats and test on the peripheral progestational activity in rats). 4. As far as the combined oral contraceptives containing estrogens and gestagens are concerned, it seems that both components are involved in the inhibition of ovulation in rats and women. There is additive synergism. 5. Conclusions concerning the activity and duration of effect in the clinic can be drawn from the intensity and duration of the progestational effect in rabbits. 6. The oral and subcutaneous activity of estrogens in different tests in rats and mice is in parts very well correlated. This is also true for the antiovulatory activity. 7. Comparison of the estrogenic activity of ethinyl estradiol and mestranol in rats, mice and women still leaves the question unanswered whether ethinyl estradiol is more potent than mestranol. 8. Certain conclusions regarding the depot effect in the clinic can be drawn from the duration of the estrogenic activity in the Allen-Doisy test. This test is at least suitable for the selection of the optimal depot estrogen. 9. As concerns androgens, clinical dose finding is so difficult because there are no or only poor clinical parameters for androgenicity. The oral evaluation of androgens in rats and mice provides no evidence for whether or not an androgen is orally active in men. Frequently, one can only resort to conclusions form analogy. 10. The duration of androgenic activity in rats allows certain conclusions to be drawn regarding the duration of activity in men. Dose finding, however, is difficult. 11. Steroids in which the anabolic and androgenic activity in the levator ani muscle/accessory sexual gland test are dissociated (anabolics) do also show dissociation of these two partial activities in the clinic. 12. The levator ani muscle/accessory sexual gland test in rats allows also conclusions to be drawn as to the depot activity in the clinic. 13...
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PMID:[Problems of dose finding: sexual hormones (author's transl)]. 57 80

The effects of norethindrone (NEI), norethandrolone (NEA), and ethinyl estradiol (EE) on liver cytochrome P-450 in rats were studied. Rats were pretreated with phenobarbitone sodium (80 mg/kg for 3 days), 3-methyl cholanthrene (20 mg/kg for 3 days), and pregnenolone 16alpha-carbonitrite (75 mg/kg twice daily for 3 days). NEI, NEA, and EE were given at a dose of 100 mg/kg. Liver microsomal fractions were prepared and determinations of cytochromes P-450 and b5 made. Steroids were also incubated with liver mitochondrial preparations and P-450 measured. Liver porphyrins were determined as were mitochondrial 5-aminolaevulinate synthase activity. Isolation of green pigments was undertaken. NEI and EE caused a time-dependent loss of cytochrome P-450 when incubated in vitro with rat microsomal fractions and NADPH-generating systems. The effect of pretreatment of rats with inducers of mixed-function oxidases on the steroid mediated loss of cytochrome P-450 in vitro were: 1) phenobarbitone stimulated P-450 breakdown, 2) methylcholanthrene-induced cytochrome P-448 was unaffected, and 3) pregnenolone was without effect. The enzyme system involved in the NEI breakdown of P-450 has many of the characteristics of the microsomal mixed-function oxidases. In vivo, there was a marked decrease in P-450 (52%) after a single injection of NEI. Cytochrome b5 was minimally affected. Loss of P-450 was accompanied by increasing porphyrin levels. NEI, NEA, and EE caused a 3.2-fold induction of 5-aminolaevulinate synthase activity. Rats pretreated with phenobarbitone and given NEI or EE formed green pigments. While metabolic pathways differ between the species, it is suggested that long-term estrogen therapy might predispose some individuals to the type of porphyria associated with the side effects of these compounds.
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PMID:Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol. 90 18

4 male transsexuals, aged 23-46 years, were treated with ethinyl estradiol (1-2 mg daily) for at least 12 months prior to orchiectomy and sex-change surgery. The pattern of in vitro steroid biosynthesis by testicular tissue before and after this therapy was examined histologically and hormonally. Serum follicle stimulating hormone and luteinizing hormone were measured by radioimmunoassay as were plasma and testicular concentrations of testosterone (T). Plasma estradiol (E) and testicular progesterone (P) were also measured. In vitro steroid biosynthetic studies were made with radiolabeled precursors. Histology showed a uniform picture of spermatogenic arrest at the primary spermatocyte level after treatment. Concentrations of T, P, E, and 20alpha-dihydroxyprogesterone in the testes of the treated men showed that all hormones except E decreased markedly. Biosynthesis studies demonstrate that radioactive P substrate was poorly metabolized. In vitro synthesis of T from P was severely impaired; 17alpha-hydroxylation decreased substantially while 20alpha-hydroxy-steroid-dehydrogenase activity increased after estrogen treatment. It is suggested that 17alpha-hydroxylase activity is either under gonadotropin regulation or is directly inhibited by estrogen treatment. The increase in 20alpha-reduction might represent an alternate pathway unaffected by the treatment.
Steroids 1977 Jun
PMID:In vitro steroid metabolic studies in human testes I: Effects of estrogen on progesterone metabolism. 91 Feb 50

The methods of synthesis of the 6-(0-carboxymethyl) oxime derivative of 6-oxoethynylestradiol-17beta, the 3-succinyl derivative of ethiny estradiol-17beta and the 3-carboxymethyl oxime derivative of norethindrone and norgestrel as well as the synthesis of the corresponding bovine serum albumin (BSA) conjugates required for the specific antisera for mestranol, ethinyl estradiol, norethindrone, and norgestrel in rabbits are described. The synthesis of 6-(0-carboxymethyl) oxime derivative involves a 4-step synthesis and a chromatographic purification which is an improvement over past methods. Conjugation to BSA was by the carbodiimide method. Response of immunization was measured in terms of titer, association constant, and cross-reactivity as a function of time after immunization with 3 dose levels of each antigen. Titer response was independent of dose for the original injection. Ethiny estradiol-3-conjugates had very low titers.
Steroids 1977 Jul
PMID:Production of antisera against contraceptive steroids. 91 17

The biliary metabolites of tritiated-6,7-estriol were identified following the administration of the estrogen to rats. Glucosiduronate conjugate fraction constituted approximately 70% of the excreted metabolites. The primary metabolite found in this conjugate fraction was 3,17beta-dihydroxy-2-methoxy-1,3,5(10)-estratrien-16-one. There were also significant amounts of 3,17beta-dihydroxy-1,3,5,(10-estratrien-16-one and 2,3,17beta-trihydroxy-1,3,5(10)-estratrien-16-one. Smaller amounts of 1,3,5(10)-estratriene-2,3,16alpha,17beta-terol and 2-methoxy-1,3,5(10)-estratriene-3,16alpha,17beta-triol were also present. The administration of 17alpha-ethinyl estradiol reduced the rate of excretion of radioactivity and the proportion of 16-oxo-17-beta-ol metabolites in the glucosiduronate fraction.
Steroids 1976 May
PMID:Biliary metabolites of estriol in the rat. 94 Nov 79

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

Using both pulse injections and constant infusions of 3-H-mestranol (3H-ME) (1) and 3-H-ethinyl estradiol (3H-EE) we have studied the metabolism of these compounds in non-users and users of oral contraceptives. Following pulse injection of 3-H-ME the disappearance of radioactivity could be described as a function which was the sum of two exponentials. Studied by both types of administration there was no difference in the metabolism of 3H-ME in the two groups; the overall mean plus or minus SE metabolic clearance rate (MCRM) was 690 plus or minus 45 1/day/m2, the mean ratio of the concentrations of radioactivity as EE following administration of ME (CRM-BB,E) was 0.23 plus or minus 0.02 and the mean (p)M,EBB (fraction of administered ME measured in blood as EE) was 0.19 (95% confidence limits equals 0.15 - 0.23). Following pulse injection of 3-H-EE the disappearance of radioactivity was best described as a function which is the sum of three exponentials. Results from both types of administration revealed no difference in the metabolism of 3H-EE between non-users. The overall mean plus or minus SE MCREE was 630 plus or minus 30 1/day/M2. The MCREE is significantly (0.02 greater than P greater than 0.01) less than the mean MCR for estradiol reported previously, in both non-users and users of oral contraceptives. The use of oral contraceptives containing estrogens and progestins does not appear to influence the metabolism of the estrogen used. Approximately 20% of mestranol is converted to and appears in the blood as ethinyl estradiol.
Steroids 1975 Jan
PMID:The metabolism of synthetic estrogens in non-users and users of oral contraceptives. 111 Nov 71


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