Journal of steroid biochemistry最新文献

{"title":"Testing for fluoxymesterone (Halotestin®) administration to man: Identification of urinary metabolites by gas chromatography-mass spectrometry","authors":"R.Craig Kammerer,&nbsp;James L. Merdink,&nbsp;Mark Jagels,&nbsp;Don H. Catlin,&nbsp;Ka Kit Hui","doi":"10.1016/0022-4731(90)90185-U","DOIUrl":"10.1016/0022-4731(90)90185-U","url":null,"abstract":"<div><p>Fluoxymesterone, an anabolic steroid, is metabolized in man primarily by 6β-hydroxylation, 4-ene-reduction, 3-keto-reduction, and 11-hydroxy-oxidation. These pathways of metabolism are suggested by the positive identification of 4 metabolites and the tentative identification of 3 other metabolites. Detection of the drug in urine is possible for at least 5 days after a single 10 mg oral dose to previously untreated adult males, by monitoring the presence of 2 metabolites, since the parent drug is not detectable more than 1 day after the dose.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 659-666"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90185-U","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum cortisol in adrenal hirsutism as estimated by five different methods","authors":"Janet Brotherton,&nbsp;Birgit Rothbart","doi":"10.1016/0022-4731(90)90183-S","DOIUrl":"10.1016/0022-4731(90)90183-S","url":null,"abstract":"<div><p>Serum cortisol had been estimated in 152 hirsute women complaining of fertility problems, of whom 36 were subsequently diagnosed as having adrenal hirsutism and 10 as having congenital adrenal hyperplasia (steroid 21-hydroxylase deficiency), using five methods: an in-house tritium radioimmunoassay after extraction with ethanol; the Diagnostic Products Corp. “Coat-a-count” iodinated direct radioimmunoassay; the Pharmacia-LKB “DELFIA” lanthanum-enhanced fluoroimmunoassay; the Amersham “Amerlite” luminescence immunoassay; and the Walker “Synelisa” enzyme-linked immunoassay. Although stripped pool serum samples containing weighed amounts of cortisol produced acceptable values in all assays, the patient samples showed a number of high results, much greater than the accepted normal upper limit of 250 ng/ml (25 /μg/dl, 690 nmol/1). This was especially so in 21-hydroxylase deficiency, when cortisol values should be very low. Only the luminescence and iodinated assays produced very low values after dexamethasone suppression. After the outliers had been excluded, only the iodinated assay showed a good statistical agreement with the more elaborate tritium assay. The most specific assay was the luminescence method, which produced generally lower results in most cases. This was selected as the new routine method. The unreliable cortisol results in adrenal hirsutism are attributed to high cross-reaction of the antiserum in each of the assays with 17-hydroxyprogesterone, progesterone and 21-deoxyderivatives of cortisol and deoxycorticosterone. In general, all standard and commercially available cortisol assays appears to be unsuitable for cortisol estimation in 21-hydroxylase deficiency, and probably also for neonates.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 641-649"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90183-S","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effect of a new androstenedione derivative, 14α-hydroxy-4-androstene-3,6,17-trione (14α-OHAT) on aromatase activity of human uterine tumors","authors":"Takara Yamamoto ,&nbsp;Masaaki Fukuoka ,&nbsp;Yasuko Fujimoto ,&nbsp;Jo Kitawaki ,&nbsp;Masamichi Nakakoshi ,&nbsp;Makoto Yoshihama ,&nbsp;Hiroji Okada","doi":"10.1016/0022-4731(90)90167-Q","DOIUrl":"10.1016/0022-4731(90)90167-Q","url":null,"abstract":"<div><p>The development of human uterine estrogen-dependent tumors is considered to be closely related to estrogen biosynthesis. This study examined whether or not 14α-hydroxy-4-androstene-3,6,17-trione (14α-OHAT), a new 4-androstene-3,17-dione derivative synthesized microbiologically, inhibits estrogen biosynthetase (aromatase) activities of human uterine tumors (i.e. uterine endometrial cancer, uterine leiomyoma and uterine adenomyosis tissues).</p><p>14α-OHAT inhibited aromatase activity in all uterine tumors, dose-dependently (0.1–10 μM).</p><p>Moreover, 14α-OHAT did not show the binding affinity to rabbit uterine cytosol-sex steroids, and it was not converted to estrogen in human placental preparations. p]Thus, 14α-OHAT, an aromatase inhibitor, may be useful clinically as an endocrine chemotherapy for peri- or post-menopausal women with uterine estrogen-dependent tumors.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 517-521"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90167-Q","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13367571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of calcium on progesterone production in small and large bovine luteal cells","authors":"H.W. Alila ,&nbsp;J.S. Dayis ,&nbsp;J.P. Dowd ,&nbsp;R.A. Corradino ,&nbsp;W. Hansel","doi":"10.1016/0022-4731(90)90189-Y","DOIUrl":"10.1016/0022-4731(90)90189-Y","url":null,"abstract":"<div><p>We studied the effects of calcium (Ca²⁺) ions in progesterone (P) production by separated small and large luteal cells. Corpora lutea were collected from 31 heifers between days 10 and 12 of the estrous cycle. Purified small and large cells were obtained by unit gravity sedimentation and flow cytometry. P accumulation in cells plus media was determined after incubating 1 × 10⁵ small and 5 × 10³ large cells for 2 and 4 h respectively. Removal of Ca²⁺ from the medium did not influence basal P production in the small cells (<em>P</em> &gt; 0.05). However, stimulation of P by luteinizing hormone (LH), prostaglandin E₂ (PGE₂), 8-bromo-cyclic 3',5' adenosine monophosphate (8-Br-cAMP) and prostaglandin F₂α (PGF₂α) was impaired (<em>P</em> &lt; 0.05) by low Ca²⁺ concentrations. LH and PGE₂-stimulated cAMP production was not altered by low extracellular Ca²⁺ concentrations, and PGF₂α had no effect on cAMP. In contrast, basal as well as LH and forskolin-stimulated P production were attenuated (<em>P</em> &lt; 0.05) in Ca²⁺-deflcient medium in the large cells. However, P production stimulated by 8-Br-cAMP was not altered in Ca²⁺-deficient medium. Steroidogenesis in large cells was also dependent on intracellular Ca²⁺, since 8-<em>N</em>, <em>N</em>-diethylamineocytyl-3,4,5-trimethoxybenzoate (TMB-8), an inhibitor of intracellular Ca²⁺ release and/or action, suppressed (<em>P</em> &lt; 0.05) basal, LH and 8-Br-cAMP stimulated P. In contrast, basal P in small cells was not altered by TMB-8; whereas LH-stimulated P was reduced 2-fold (<em>P</em> &lt; 0.05). The calcium ionophore, A23187, inhibited LH-stimulated P in small cells and both basal and agonist-stimulated P in large cells. These studies show that basal P production in small cells does not require Ca²⁺ ions, while hormone-stimulated P production in small cells and both basal and hormone-stimulated P in large cells do require Ca²⁺. The inhibitory effect of Ca²⁺ ion removal was exerted prior to the generation of cAMP in the large cells, but distal to cAMP generation in hormone-stimulated small cells. The calmodulin/protein kinase C antagonist, W-7, also inhibited both basal and hormone-stimulated P production in both small and large luteal cells, indicating that P production in luteal cells also involves Ca²⁺-calmodulin/protein kinase C-dependent mechanisms.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 687-693"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90189-Y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13323704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro inhibition by ketoconazole of human testicular steroid oxidoreductases","authors":"Yotsuo Higashi,&nbsp;Ken-Ichiro Yoshida ,&nbsp;Hiroyuki Oshima","doi":"10.1016/0022-4731(90)90186-V","DOIUrl":"10.1016/0022-4731(90)90186-V","url":null,"abstract":"<div><p>An oral antimycotic agent, ketoconazole has been demonstrated to be an inhibitor of cytochrome <em>P</em>-450-dependent monooxygenases. To investigate its effect on steroid oxido-reductases, <em>in vitro</em> studies were carried out using subcellular fractions of human testes. Ketoconazole competitively inhibited activities of 3β-hydroxy-5-ene-steroid oxidoreductase/ isomerase and NADH-linked 20α-hydroxysteroid oxidoreductase for steroid substrate and the <em>K</em>_<em>i</em> values were 2.9 and 0.9 μM, respectively. In contrast, ketoconazole inhibited neither 17β-hydroxysteroid oxidoreductase nor NADPH-linked 20α-hydroxysteroid oxido-reductase, indicating that the two 20α-hydroxysteroid oxidoreductases are distinct. Further, ketoconazole inhibited non-competitively the above enzyme activities for the corresponding cofactors of NAD and NADH. From the binding mode of ketoconazole to cytochrome <em>P</em>-450 and the present findings, it appears likely that the agent binds to a site which is different from that of steroids or pyridine nucleotides.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 667-671"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90186-V","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro synthesis of 16α-hydroxyestrone by female rat liver microsomes: Its possible role in the etiology of breast cancer","authors":"C.J.M. Arts ,&nbsp;J.W.G.M. Wilmer ,&nbsp;A.Th.H.J. De Bie ,&nbsp;H. Van Den Berg","doi":"10.1016/0022-4731(90)90169-S","DOIUrl":"10.1016/0022-4731(90)90169-S","url":null,"abstract":"<div><p>Liver homogenates from female rat strains (Sprague-Dawley, Wistar and Fisher) were incubated in a NADPH regenerating medium in the presence of labelled and unlabelled estrone. Liver microsomes isolated from male rats and female mice were used as positive controls. Using HPLC and paper chromatography, under the experimental conditions used it was found that liver homogenates from female rats were able to convert estrone to various metabolites such as 16α-hydroxyestrone. In a mutagenicity assay (Ames test), with 16α-hydroxyestrone as test substance, two strains (TA98 and TA 1538) of the five strains tested showed a 2–3-fold increase in the number of his⁺ revenants relative to the control values. Estrone did not cause any mutagens in the test used.</p><p>It is concluded that female rats are able to synthesize 16α-hydroxyestrone <em>in vitro</em>. Whether this compound is risk factor for breast cancer remains unclear.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 527-531"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90169-S","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13367573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic polymorphism of the human sex hormone-binding globulin: Evidence of an isoelectric focusing variant with normal androgen-binding affinities","authors":"Fernando Larrea ,&nbsp;Rosa Maria Oliart ,&nbsp;Julio Granados ,&nbsp;Osvaldo Mutchinick ,&nbsp;Vicente Diaz-Sanchez ,&nbsp;Neal A. Musto","doi":"10.1016/0022-4731(90)90171-N","DOIUrl":"10.1016/0022-4731(90)90171-N","url":null,"abstract":"<div><p>Human sex hormone-binding globulin (hSHBG) is a plasma glycoprotein composed of two identical subunits. The protein, which has high affinity for testosterone and estradiol has been purified to homogeneity. In this study we have investigated, on neuraminidase-treated serum samples, the presence of genetic variations of hSHBG by polyacrylamide gel isoelectric focusing (IEF).</p><p>Based on IEF analyses of 110 serum samples from adult Mexican individuals we have identified two distinct IEF-patterns. The most frequent phenotype (95.45%) was characterized by two IEF-bands with pIs of 6.50 and 6.63, respectively. In five serum samples, a different 4-band pattern with pis of 6.50, 6.63, 6.70 and 6.76 was identified. Family studies showed that this pattern was genetically determined. The frequency of this variant was 4.55%, and the observed phenotypes were consistent with the expression of an autosomal genetic system. The estimated gene frequencies for both alleles were shown to be in genetic equilibrium. Affinity constants, binding kinetics and serum concentrations of hSHBG from individuals having a 4-band pattern were similar to those obtained in individuals with a 2-band pattern, thus suggesting that the mechanism responsible for the generation of polymorphic variants of hSHBG reported herein did not involve the steroid binding site of the molecule. These findings may be of broad interest, as other serum binding proteins express genetic variants, which may permit their further structural and functional subclassification.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 541-548"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90171-N","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greater conversion of testosterone to 5α-dihydrotestosterone, reflecting increased peripheral 5α-reductase activity in nude mice treated with high doses of cyclosporine A","authors":"Philippe Boudou ,&nbsp;Jean Fiet ,&nbsp;Patrick Vexiau ,&nbsp;Jean-Marie Villette ,&nbsp;Noah Hardy ,&nbsp;Claude Dreux","doi":"10.1016/0022-4731(90)90178-U","DOIUrl":"10.1016/0022-4731(90)90178-U","url":null,"abstract":"<div><p>Following cyclosporine A (CsA) immunosuppressive therapy in kidney grafts, increased body hair growth (hypertrichosis and/or hirsutism) without significant variation in normal circulating plasma androgen levels (as observed in idiopathic hirsutism) has been reported by several authors. Other authors have described increased hair growth in nude mice treated with CsA. In order to evaluate the action of this drug in target tissues, using dorsal skin homogenates from nude mice treated with various doses of CsA, we measured the metabolic conversion of testosterone (T) to its 5α-reduced products, reflecting 5α-reductase activity (5α-RA). Three groups of 5 female nude mice were treated with an oral suspension containing CsA 5 mg/kg (group 1), 25 mg/kg (group 2) and 100 mg/kg (group 3), respectively, and the results, including 5a-DHT and Adiol formation, were compared with those obtained in a control group (<em>n</em> = 5) receiving only the olive oil vehicle. Cutaneous metabolic conversion of T was determined using tritiated T as substrate. After l h of incubation, 5α-DHT and other 5α-reduced products formed were separated and quantified using a reverse-phase chromatography column fitted to a flow-through radioactivity detector. Mean ± SD 5α-DHT formation (expressed as pmol per 100 mg of protein per h) was found to be increased in the treated groups (group 1: 3.17 ± 0.37, group 2: 3.10 ± 0.13, group 3: 4.26 ± 0.20), respectively 7.5% (NS), 5.10% (NS) and 44.4% (<em>P</em> = 0.01) higher than in the control group (2.95 ± 0.13). In addition to 5α-DHT, enhanced formation of A4-androstenedione (A4), 5α-androstan-3β,17β-diol (3β-diol) and 5α-androstan-3α,170-diol (3α-diol) were also observed in the treated groups. These results show a significantly increased formation of 5α-DHT (and Adiol) in nude mice treated with high dose-levels of CsA.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 597-601"},"PeriodicalIF":0.0,"publicationDate":"1990-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90178-U","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiandrogen ICI 176,334 does not prevent development of androgen insensitivity in S115 mouse mammary tumour cells","authors":"Philippa D. Darbre ,&nbsp;R.J.B. King","doi":"10.1016/0022-4731(90)90078-7","DOIUrl":"10.1016/0022-4731(90)90078-7","url":null,"abstract":"<div><p>Many forms of endocrine therapy for steroid-sensitive tumours involve regimes of steroid agonist deprivation by administration of steroid antagonists. The partial or short-lived response to such therapy results from the inevitable progression of the tumour cells to a state of steroid insensitivity. Several cell culture systems have shown that steroid ablation results in loss of steroid sensitivity and we have used an <em>in vitro</em> model here to study the influence of steroid antagonists on this progression. Growth of androgen-responsive S 115 mouse mammary tumour cells in the long-term absence of steroid results in a loss of androgen-sensitivity. We have studied here the effects of the pure antiandrogen ICI 176,334 on the growth of S 115 cells and on their progression to steroid autonomy. Although a pure antiandrogen in its action on these cells with very low toxicity, it had no protective effect against loss of cellular or molecular androgen-responsive parameters. The clinical implications for endocrine therapy are discussed.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 5","pages":"Pages 385-389"},"PeriodicalIF":0.0,"publicationDate":"1990-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90078-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13367670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxylated triphenylacrylonitriles adopt a unique orientation within the binding site of the estrogen receptor","authors":"M. Pons ,&nbsp;E. Bignon ,&nbsp;A.Chastes De Paulet ,&nbsp;J. Gilbert ,&nbsp;T. Ojasoo ,&nbsp;J.P. Raynaud","doi":"10.1016/0022-4731(90)90079-8","DOIUrl":"10.1016/0022-4731(90)90079-8","url":null,"abstract":"<div><p>The relative binding affinities of a series of twelve <em>para</em>-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. A hydroxyl group in a given position always interacts with the same location within the site.</p><p>Mono-hydroxylation of the highly hydrophobic non-substituted TPE skeleton led to a large increase in relative binding affinity for ER which could be explained by a dual mechanism whereby the interaction specific to the hydroxyl is accompanied by a temperature- or time-dependent binding process that is not related to the hydroxylation position.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 5","pages":"Pages 391-397"},"PeriodicalIF":0.0,"publicationDate":"1990-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90079-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13367671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}