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Journal of Steroid Biochemistry

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https://www.readbyqxmd.com/read/2214780/potential-bile-acid-precursors-in-plasma-possible-indicators-of-biosynthetic-pathways-to-cholic-and-chenodeoxycholic-acids-in-man
#1
M Axelson, J Sjövall
The plasma concentrations of 3 beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid have been compared with that of 7 alpha-hydroxy-4-cholesten-3-one in healthy subjects and in patients with an expected decrease or increase of the bile acid production. In controls and patients with liver disease, the level of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid was positively correlated to that of 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and not to that of 7 alpha-hydroxy-4-cholesten-3-one...
August 28, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2214774/17-beta-hydroxysteroid-oxidoreductase-activity-age-dependent-profile-in-rat-liver-and-kinetic-properties-of-the-hepatic-microsomal-enzyme-in-relation-to-cytochrome-p450-dependent-steroid-hydroxylation
#2
M Murray, B P Horsfield
The functional relationship between the microsomal cytochrome P450 and 17 beta-hydroxysteroid oxidoreductase (HSOR) enzymes involved in steroid metabolism was investigated in rat liver. In male and female rat hepatic microsomes the NADPH-dependent conversion of androstenedione (AD) to testosterone (T) was approx. 4-fold greater at 6 weeks of age than in 1 week old animals. In hepatic microsomes from 15 week old rats the activity of the HSOR pathway was greater in males than in females (1.51 compared to 0.80 nmol T formed/min/mg protein)...
August 28, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2214759/hydroxylated-triphenylacrylonitriles-adopt-a-unique-orientation-within-the-binding-site-of-the-estrogen-receptor
#3
M Pons, E Bignon, A Crastes de Paulet, J Gilbert, T Ojasoo, J P Raynaud
The relative binding affinities of a series of twelve para-hydroxylated triphenylethylenes (TPEs) for the estradiol receptor (ER) of calf uterus cytosol were measured by a competition method. The results obtained under equilibrium conditions support the hypothesis of the additivity of the energies corresponding to each of the hydrogen-bond type interactions of di- or tri-hydroxylated TPEs with the estradiol binding site of ER and strongly suggest that, whichever ring is hydroxylated, the orientation of the TPE in the steroid binding site is always the same...
August 14, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2391957/antagonism-of-estrogen-and-antiestrogen-induced-uterine-complement-component-c3-expression-by-ici-164-384
#4
M S Galman, S A Sundstrom, C R Lyttle
The uterus of the immature rat synthesizes and secretes complement component C3 in response to estradiol treatment. This response occurs in the uterine epithelial cells and is also stimulated by several antiestrogens including tamoxifen and LY117018. The administration of a new antiestrogen ICI 164,384 blocked the estradiol as well as the antiestrogen-stimulated increases in uterine weight, epithelial cell height, C3 synthesis and C3 mRNA. ICI 164,384 demonstrated no agonist properties in terms of epithelial cell response as determined by C3 expression...
July 4, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2168008/effect-of-atp-on-the-regulation-of-the-steroid-binding-activity-of-the-oestradiol-receptor
#5
H Lahooti, T Thorsen, A Aakvaag
We have observed that ATP induces a second type of oestradiol binding site with slightly lower affinity (Ka 3.3 x 10(8) M-1) and lower sedimentation coefficient (4 S) in cytosol from immature lamb uterus and MCF-7 cells. A factor isolated from immature lamb uterine nuclear extract was found to decrease the steroid binding activity of oestradiol receptor that had been purified by heparin Sepharose and oestradiol-Sepharose chromatography. Inhibition of this factor by known phosphatase inhibitors, indicated that this factor may be a phosphatase...
July 4, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2142232/in-vitro-and-in-vivo-binding-of-toremifene-and-its-metabolites-in-rat-uterus
#6
COMPARATIVE STUDY
N H Simberg, J T Murai, P K Siiteri
The in vitro binding affinities of toremifene (TOR), 4-hydroxy toremifene (4-OH-TOR) and several other metabolites for the rat uterine cytosolic estrogen receptor were compared with those of tamoxifen (TAM) and 4-hydroxy tamoxifen (4-OH-TAM). Only small differences were observed and the binding affinities of both 4-hydroxy metabolites were similar to that of estradiol (E2). Uterine uptake and subcellular distribution of [3H]TOR and [3H]TAM were then compared at 1, 8 and 72 h after administration to castrated rats...
June 22, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2142231/review-of-the-pharmacological-properties-of-toremifene
#7
REVIEW
L Kangas
New compounds were synthesized with the aim to develop new anti-estrogenic antitumor drugs. The biological properties of the molecules were screened by (1) estrogen receptor (ER) binding, (2) effect on MCF-7 cells, (3) uterotrophic effect and inhibition of estradiol induced uterotropic effect and (4) antitumor effect in DMBA induced rat mammary cancer. One of the molecules, Fc-1157a = toremifene, exhibited the following characteristics: competitive inhibition of [3H]estradiol binding to ER (IC50 = 0.3 mumol/l), inhibition of MCF-7 cell growth in a concentration-dependent manner and cell-killing effect at higher than 3 mumol/l concentrations...
June 22, 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2362446/formation-of-progesterone-and-1-dehydroprogesterone-from-cholesterol-in-fermentation-cultures-of-mycobacterium-aurum
#8
C Hörhold, K H Böhme
The formation of progesterone and 1-dehydroprogesterone from cholesterol in fermentation cultures of Mycobacterium aurum ATCC 25790 was studied with the aim of clarifying the microbial pathway. The C22-intermediate (20S)-20-carboxy-1,4-pregnadien-3-one was microbiologically converted via the undetectable corresponding aldehyde into the C22-alcohol. However in the fermentation broth without microorganisms, but containing 2,2'-bipyridyl and copper ions, synthetically prepared C22-aldehyde was oxidized to the corresponding C21-compound 1-dehydroprogesterone, suggesting that the enzymatically originated C22-aldehydes may be immediately chemically oxidized to the corresponding C21-ketones...
June 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2362436/synthesis-and-biological-activity-of-4-methylestradiol
#9
X D Qian, Y J Abul-Hajj
The synthesis of 4-methylestradiol (4-ME2) was carried out by reductive aromatization of 4-methyl-1,4-androstadiene-3-one-17 beta-ol. The relative binding affinity of 4-ME2 was found to be 10 and 25% of estradiol at 0 and 25 degrees C, respectively. 4-ME2 had considerably weaker uterotrophic activity relative to estrone and was found to have no antiuterotrophic activity.
May 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2362426/the-synthesis-of-e-17-alpha-131i-iodo-vinyl-oestradiol-and-evaluation-of-its-use-as-a-radiotracer-for-oestrogen-receptor-positive-breast-tumours
#10
E K Symes, W F Coulson, R Das, J H Scurr
17 alpha-Iodo-vinyl oestradiol binds with high affinity to the oestrogen receptor, is metabolically stable and has been shown to accumulate in oestrogen sensitive tissues of rodents. We have synthesised this compound and its 3-acetate, labelled with carrier free 125I and shown the accumulation of both compounds in rat uterus. 17 alpha-Iodo-vinyl oestradiol-3-acetate was prepared labelled with carrier free 131I and administered to twelve patients with suspected breast cancer, approximately 1 h before surgical removal of the primary tumour mass...
May 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2194075/reasons-for-reduced-activities-of-17-alpha-hydroxylase-and-c17-c20-lyase-in-spite-of-increased-contents-of-cytochrome-p-450-in-mature-rat-testis-fetally-irradiated-with-60co
#11
H Inano, H Ishii-Ohba, K Suzuki, K Ikeda
Pregnant rats received whole body irradiation with 2.6 Gy gamma-ray from a 60Co source at Day 20 of gestation. When pups were 4 months old, activities of electron transport system and steroid monooxygenase in tests were assayed. The content of total cytochrome P-450 in the irradiated testes had increased to 170% of that in non-irradiated rats, but NADPH-cytochrome P-450 reductase activity had reduced to 36% of the control. Also, amounts of cytochrome b5 in testicular microsomal fraction were decreased markedly after irradiation, but no significant change of NADH-cytochrome b5 reductase activity was observed in the treated pups...
May 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2325409/pronounced-and-differential-effects-of-ionic-strength-and-ph-on-testosterone-oxidation-by-membrane-bound-and-purified-forms-of-rat-liver-microsomal-cytochrome-p-450
#12
B Gemzik, M R Halvorson, A Parkinson
The aim of this study was to determine the effects of ionic strength and pH on the different pathways of testosterone oxidation catalyzed by rat liver microsomes. The catalytic activity of cytochromes P-450a (IIA1), P-450b (IIB1), P-450h (IIC11) and P-450p (IIIA1) was measured in liver microsomes from mature male rats and phenobarbital-treated rats as testosterone 7 alpha-, 16 beta-, 2 alpha- and 6 beta-hydroxylase activity, respectively. An increase in the concentration of potassium phosphate (from 25 to 250 mM) caused a marked decrease in the catalytic activity of cytochromes P-450a (to 8%), P-450b (to 22%) and P-450h (to 23%), but caused a pronounced increase in the catalytic activity of cytochrome P-450p (up to 4...
March 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2325408/a-comparative-study-of-the-interaction-of-oestradiol-and-the-steroidal-pure-antioestrogen-ici-164-384-with-the-molybdate-stabilized-oestrogen-receptor
#13
COMPARATIVE STUDY
A P Wilson, P J Weatherill, R I Nicholson, P Davies, A E Wakeling
The kinetics of binding of oestradiol and the steroidal pure antioestrogen ICI 164,384 to the molybdate-stabilized oestrogen receptor, partially purified from pig and human uterine tissue, were determined. ICI 164,384 bound directly to the oestrogen receptor protein and the kinetic parameters of this interaction were, in general, similar to those for the binding of oestradiol, regardless of the source of the receptor protein. However, the rate of association of oestradiol, regardless of the source of the receptor protein...
March 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2308345/coordinated-induction-of-estrogen-hydroxylase-and-catechol-o-methyl-transferase-by-xenobiotics-in-first-trimester-human-placental-explants
#14
E R Barnea, S Avigdor
The estrogen phenol A-ring metabolism was investigated in the first trimester placenta using radioenzymatic techniques. In untested explants cultured for 16 h, estrogen hydroxylase (EH) but not catechol-O-methyl transferase (COMT) activity was increased significantly 1.8-fold (P less than 0.05). Cultures made in the presence of chemoprotectors, 25 microM of 1-phenylazo-2-naphthol (Sudan I) and coumarin but not 2(3)-tert-butyl-4-hydroxyanisole (BHA) caused a significant increase in EH activity, 1.8- and 2.2-fold, respectively (P less than 0...
February 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2155352/effects-of-various-inducers-on-diethylstilbestrol-metabolism-drug-metabolizing-enzyme-activities-and-the-aromatic-hydrocarbon-ah-receptor-in-male-syrian-golden-hamster-liver
#15
G Blaich, M Göttlicher, P Cikryt, M Metzler
In order to elucidate the role of metabolic activation of the synthetic estrogen, diethylstilbestrol (DES), in the mechanism of liver tumor formation in male Syrian golden hamsters observed after combined treatment with DES and 7,8-benzoflavone (7,8-BF), the metabolism of DES and the concentrations and activities of various drug-metabolizing enzymes were studied in hamster liver microsomes after various pretreatments. The levels of the hepatic aromatic hydrocarbon (Ah) receptor were also determined. Pretreatment with 7,8-BF increased both P450 and cytochrome b5 levels, whereas phenobarbital (PB) and 3-methylcholanthrene (MC) induced P450 but not cytochrome b5...
February 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2407900/differential-effects-of-ovarian-steroids-and-triphenylethylene-compounds-on-macromolecular-uptake-and-thymidine-incorporation-in-the-mouse-uterus
#16
COMPARATIVE STUDY
Y M Huet-Hudson, S K Dey
In the rodent uterus, estrogen elicits a biphasic response i.e. an early phase (Phase I) and a late phase (Phase II). Estradiol-17 beta (E2) and estriol (E3), as well as triphenylethylene (TPE) compounds, CI-628 and clomiphene citrate (CC), were used to characterize Phase I and Phase II responses in uterine preparation for implantation in the mouse. While uterine macromolecular uptake (vascular permeability), a Phase I response, was studied in progesterone (P4)-primed animals, uterine [3H]thymidine incorporation (DNA synthesis), a Phase II response, was investigated with and without P4-priming...
January 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2308330/microsomal-dexamethasone-binding-sites-identified-by-affinity-labelling
#17
E C LaCasse, G M Howell, Y A Lefebvre
Binding studies with [3H]dexamethasone identified a class of binding sites on male rat liver microsomes. The binding sites were glucocorticoid-dependent and specific for glucocorticoids and progestins. Scatchard binding parameters, competition studies with triamcinolone acetonide, a synthetic glucocorticoid which competes well for the glucocorticoid receptor, and immunoblotting with an antiglucocorticoid receptor antibody indicated that these sites are distinct from the cytosolic glucocorticoid receptor. Affinity labelling experiments with [3H]dexamethasone 21-mesylate revealed two specifically labelled peptides, one at approx...
January 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2308321/inhibition-of-microbial-cholesterol-oxidases-by-dimethylmorpholines
#18
P G Hesselink, A Kerkenaar, B Witholt
Cholesterol oxidase is a potentially important enzyme in steroid transformations, catalysing the conversion of 3-hydroxy-5-ene steroids to 3-keto-4-ene derivatives via a 3-keto-5-ene intermediate. Morpholine derivatives, especially fenpropimorph and tridemorph, were found to block selectively the isomerisation activity of cholesterol oxidases isolated from Nocardia erythropolis, Streptomyces sp., Pseudomonas testosteroni and Schizophyllum commune. These enzymes differ strongly in physical characteristics and catalytic behaviour...
January 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2155347/catecholoestrogen-synthesis-and-metabolism-in-the-rabbit-uterus-during-the-periimplantation-period
#19
C Chakraborty, Y M Huet-Hudson, S K Dey
Microsomal oestradiol-2/4-hydroxylase (OE-2/4-H) and cytosolic catechol-O-methyltransferase (COMT) (EC 2.1.1.6) activity in the uteri of pregnant and pseudopregnant rabbits during the periimplantation period were studied. The apparent Km for the 4-hydroxylation of oestradiol (3.18 microM) was considerably less than for the 2-hydroxylation reaction (13.36 microM), whereas the Vmax were almost equal. This suggests that 4-hydroxyoestradiol (4-OH-OE2) is the predominant product of OE-2/4-H in the rabbit uterus...
January 1990: Journal of Steroid Biochemistry
https://www.readbyqxmd.com/read/2615350/regulation-of-progesterone-receptor-mrna-by-oestradiol-and-antioestrogens-in-breast-cancer-cell-lines
#20
F E May, M D Johnson, L R Wiseman, A E Wakeling, P Kastner, B R Westley
The induction of progesterone receptor mRNA by oestradiol and antioestrogens has been characterised in the MCF-7 breast cancer cell line. Progesterone receptor mRNA was induced more than 100-fold by oestradiol. The induction was half-maximal in the presence of 10(-10) M oestradiol and maximum levels were reached after 24 h treatment. Progesterone receptor mRNA was induced to 10% of the oestrogen-induced level by tamoxifen and its metabolite 4'-hydroxytamoxifen. The increase was half-maximal in the presence of 5 X 10(-8) M tamoxifen or 5 X 10(-10) M 4'-hydroxytamoxifen...
December 1989: Journal of Steroid Biochemistry
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