Journal of steroid biochemistry最新文献

{"title":"Alterations in the binding characteristics of glucocorticoid receptors from obese zucker rats","authors":"B.Douglas White,&nbsp;Roy J. Martin","doi":"10.1016/0022-4731(90)90188-X","DOIUrl":"10.1016/0022-4731(90)90188-X","url":null,"abstract":"<div><p>Obese Zucker rats appear to lack a circadian rhythm of serum corticosterone and maintain relatively high concentrations throughout the 24-h day. The binding characteristics of glucocorticoid receptors in lean and obese Zucker rats were examined in three tissues suggested to be involved in the feedback inhibition of corticosterone: the anterior pituitary, hypothalamus and hippocampus. Hepatic glucocorticoid receptors were also examined to determine if receptor alterations exist in a peripheral tissue. The dissociation constant (<em>K</em>_<em>d</em>) of glucocorticoid receptors in the anterior pituitary of obese rats was 50% greater than the <em>K</em>_<em>d</em> of receptors derived from lean rats. This suggests a decrease in the affinity of these receptors and could indicate a reduced feedback inhibition of corticosterone at the anterior pituitary. Hepatic glucocorticoid receptors of obese rats also showed an increase (150%) in the <em>K</em>_<em>d</em> of binding and a reduction (40%) in the number of receptors. No difference was observed in the <em>K</em>_<em>d</em> or maximal binding of receptors from the hypothalamus or hippocampus of lean and obese rats. It appears that glucocorticoid receptor alterations exist in obese Zucker rats and that these alterations may affect the drive of the pituitary-adrenal axis and possibly the expression of obesity.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 681-686"},"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)90188-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366614","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":"Properties of estrogen and hydroxysteroid sulphotransferases in human mammary cancer","authors":"J.B. Adams,&nbsp;N.S. Phillips","doi":"10.1016/0022-4731(90)90190-4","DOIUrl":"10.1016/0022-4731(90)90190-4","url":null,"abstract":"<div><p>Partial purification (~ χ 140-fold) of estrogen sulphotransferase (EC 2.8.2.4) in human mammary estrogen receptor positive cancer tissue was achieved by affinity chromatography on adenosine-3',5'-diphosphate-agarose. It had a <em>M</em>_<em>r</em>, of approximately 70,000 by gel filtration and upon electrophoresis on concave gradient polyacrylamide gels, showed a major (<em>M</em>_<em>r</em> 70,000) and a minor (<em>M</em>_<em>r</em> 200,000) peak of activity. Kinetics of this preparation (estradiol-17β and estrone as substrates), and also that of hydroxysteroid sulphotransferase (EC 2.8.2.2) contained in the cytosol of human mammary cancer MCF-7 cells (5-androstene-3β,17β-diol and dehydroepiandrosterone as substrates), were compared. The enzymes showed very similar behaviour, characterized by high affinity for their steroid substrates (low nM range) and co-operativity in their binding. For hydroxysteroid sulphotransferase, the adrenal-derived estrogen 5-androstene-3β,17β-diol was the preferred substrate compared to dehydro-epiandrosterone in the 0–40 nM concentration range. Such properties of the enzymes might be designed to limit the exposure of nuclear receptor to free ligand. Alternatively, a defined subcellular location would perhaps involve the enzymes in the elimination of estrogen after processing of the ligand-bound receptor.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 695-701"},"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)90190-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366615","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":"Differences in the form of the salt-transformed estrogen receptor when bound by estrogen versus antiestrogen","authors":"Mary F. Ruh,&nbsp;Jane W. Turner,&nbsp;Christine M. Paulson,&nbsp;Thomas S. Ruh","doi":"10.1016/0022-4731(90)90166-P","DOIUrl":"10.1016/0022-4731(90)90166-P","url":null,"abstract":"<div><p>Our laboratory has previously reported that antiestrogen binding to molybdate-stabilized non-transformed estrogen receptor results in a larger form of the receptor in 0.3 M KCl when compared with estrogen bound receptor. Estradiol promoted the formation of monomers in the presence of 0.3 M KC1 whereas antiestrogen appeared to promote dimer formation. We have extended these studies examining the rabbit uterine salt-transformed estrogen receptor partially purified by DEAE-cellulose chromatography. We previously demonstrated that estrogen receptor prepared in this way bound to different sites on partially deproteinized chromatin subfractions or reconstituted chromosomal protein/DNA fractions when the receptor was complexed with estrogen vs antiestrogen. Analysis of these receptor preparations indicated that DEAE-cellulose step-elution resulted in a peak fraction which sedimented as a single 5.9S peak in 5–20% sucrose density gradients containing 0.3 M KCl for receptor bound by the antiestrogens H1285 and <em>trans</em>-hydroxytamoxifen. However, receptor bound by estradiol sedimented as 4.5S. These receptor complexes bound DNA-cellulose indicating that these partially purified receptors were transformed. DEAE rechromatography or agarose gel filtration of the partially purified antiestrogen-receptor complexes resulted in significant dissociation of the larger complex into monomers. Incubations of 5.9S antiestrogen-receptor complexes with antibodies against nontransformed steroid receptor-associated proteins (the 59 and 90 kDa proteins) did not result in the interaction of this larger antiestrogen-receptor complex with these antibodies (obtained from L.E. Faber and D.O. Toft, respectively). Our results support the concept that antiestrogen binding induces a different receptor conformation which could affect monomer-dimer equilibrium, thus rendering the antiestrogen-receptor complex incapable of inducing complete estrogenic responses in target tissues.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 509-516"},"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)90166-P","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13367570","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":"Forthcoming papers in the journal of steroid biochemistry and molecular biology","authors":"","doi":"10.1016/0022-4731(90)90192-U","DOIUrl":"https://doi.org/10.1016/0022-4731(90)90192-U","url":null,"abstract":"","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Page I"},"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)90192-U","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137341070","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":"Estrophilic 3α,3β, 17β,20α-hydroxysteroid dehydrogenase from rabbit liver—I. Isolation and purification","authors":"A.N. Smirnov","doi":"10.1016/0022-4731(90)90180-Z","DOIUrl":"10.1016/0022-4731(90)90180-Z","url":null,"abstract":"<div><p>A procedure for isolation of a highly-purified estrophilic hydroxysteroid dehydrogenase (EHSD) from rabbit liver, including ammonium sulphate fractionation, gel filtration, ion-exchange and affinity chromatography on estradiol-Sepharose, has been developed. The enzyme possesses NADP-dependent 3α,3β,17β,20α-HSD activities with a wide spectrum of androgenic, progestagenic, and estrogenic substrates. EHSD is a monomeric protein whose molecular mass determined by different methods is 35,000–39,000. The protein exhibits microheterogeneity due to the differences in molecular surface charge. The catalytic and hormone-binding properties and molecular sizes of the two protein fractions obtained by chromatography on DEAE-Toyopearl are close or identical. The enzymatic activity of EHSD is minor as compared to other HSDs from rabbit liver. However, the low values of <em>K</em>_<em>m</em>, the high affinity for steroid ligands, and high tissue levels of EHSD suggest the protein to play a role in the biodynamics of sex hormones.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 609-616"},"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)90180-Z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366032","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":"7-Substituted 1,4,6-androstatriene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase","authors":"Pui-Kai Li,&nbsp;Robert W. Brueggemeier","doi":"10.1016/0022-4731(90)90170-W","DOIUrl":"10.1016/0022-4731(90)90170-W","url":null,"abstract":"<div><p>7-Phenyl-1,4,6-androstatriene-3,17-dione (<strong>4</strong>), 7-benzyl-1,4,6-androstatriene-3,17-dione (<strong>5</strong>) and 7-phenethyl-1,4,6-androstatriene-3,17-dione (<strong>6</strong>) were synthesized and evaluated <em>in vitro</em> in human placental microsomes as enzyme-activated irreversible inhibitors of aromatase. The compounds were synthesized from appropriate 7-substituted 4,6-androstadiene-3, 17-diones by reaction with DDQ under neutral conditions. All the compounds produced a first order inactivation of aromatase in the presence of NADPH but not in the absence of NADPH. Substrate 4-androstene-3, 17-dione protected the enzyme from inactivation by the inhibitors. Furthermore, cysteine failed to protect aromatase from inactivation by compounds <strong>5</strong> and <strong>6</strong>. In contrast, cysteine partially protected aromatase from inactivation by compound <strong>4</strong>. Irreversibility studies illustrated the covalent nature of the inactivation by <strong>4</strong>, <strong>5</strong> and <strong>6</strong>. The above experimental evidence demonstrated that compounds <strong>5</strong> and <strong>6</strong> are effective enzyme-activated irreversible inhibitors of aromatase.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 533-539"},"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)90170-W","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13367574","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":"Regulation of plasma corticosteroid-binding globulin in adult cynomolgus monkey (Macaca fascicularis) during different reproductive states","authors":"Marie-Laure Kottler ,&nbsp;Mauricette Domingo ,&nbsp;Joel Tardivel-Lacombe ,&nbsp;Monique Egloff ,&nbsp;Can D. Dang ,&nbsp;Herve Degrelle","doi":"10.1016/0022-4731(90)90175-R","DOIUrl":"10.1016/0022-4731(90)90175-R","url":null,"abstract":"<div><p>The plasma concentration of the corticosteroid-binding globulin (mCBG) has been measured in <em>Macaca fascicularis</em>, during different stages of reproduction and under hormonal treatments. The mCBG level was determined by a specific electroimmunoassay. There was no difference between females in the follicular phase and intact males; mCBG concentrations were respectively (mean ± SEM) 469 ± 53 and 443 ± 25.6 nmol/1. The mCBG levels were similar during both the luteal (469 ± 33.5 nmol/1) and the follicular phase (469 ± 53 nmol/1). Compared to intact males, the mCBG levels were higher (<em>P</em> &lt; 0.05) in castrated males (527 ± 6.6 nmol/1). During gestation, no systematic variations were found and the mCBG levels were not statistically different from the values found during the follicular phase. When estradiol benzoate was administered to castrated animals, the mCBG concentrations increased rapidly. In contrast, the values were reduced slightly by testosterone treatment. The sex-steroid action on the mCBG levels was discussed and compared with the mSBP levels. We question also, the mechanisms involved in the regulation of the mCBG levels during pregnancy.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 575-582"},"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)90175-R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366029","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":"Volume contents, subject index and author index (June–August 1990)","authors":"","doi":"10.1016/0022-4731(90)90194-W","DOIUrl":"https://doi.org/10.1016/0022-4731(90)90194-W","url":null,"abstract":"","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages iii-xviii"},"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)90194-W","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137341396","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":"Potential bile acid precursors in plasma—Possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man","authors":"Magnus Axelson ,&nbsp;Jan SjÖvall","doi":"10.1016/0022-4731(90)90182-R","DOIUrl":"10.1016/0022-4731(90)90182-R","url":null,"abstract":"<div><p>The plasma concentrations of 3β-hydroxy-5-cholestenoic acid, 3β,7α-dihydroxy-5-cholestenoic acid and 7α-hydroxy-3-oxo-4-cholestenoic acid have been compared with that of 7α-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 7α-hydroxy-3-oxo-4-cholestenoic acid was positively correlated to that of 3β,7α-dihydroxy-5-cholestenoic acid and not to that of 7α-hydroxy-4-cholesten-3-one. In patients with stimulated bile acid formation the levels of the acids were not correlated to each other but there was a significant positive correlation between the levels of 7α-hydroxy-3-oxo-4-cholestenoic acid and 7α-hydroxy-4-cholesten-3-one. These findings indicate that the precursor of 7α-hydroxy-3-oxo-4-cholestenoic acid differs depending on the activity of cholesterol 7α-hydroxylase. Since the activity of this enzyme is reflected by the level of 7α-hydroxy-4-cholesten-3-one in plasma the findings are compatible with a formation of 7α-hydroxy-3-oxo-4-cholestenoic acid from 3β,7α-dihydroxy-5-cholestenoic acid when the rate of bile acid formation is normal or reduced and from 7α-hydroxy-4-cholesten-3-one under conditions of increased bile acid synthesis. In support of this interpretation, 7α,26-dihydroxy-4-cholesten-3-one was identified at elevated levels in plasma from patients with ileal resection or treated with cholestyramine. The levels of 7α,12α-dihydroxy-4-cholesten-3-one were also higher than normal in these patients.</p><p>Based on these findings and previous knowledge, a model is proposed for the biosynthesis of bile acids in man. Under normal conditions, two major pathways, one “neutral” and one “acidic” or “26-oxygenated”, lead to the formation of cholic acid and chenodeoxycholic acid, respectively. These pathways are separately regulated. When the activity of cholesterol 7α-hydroxylase is high, the “neutral” pathway is most important whereas the reverse is true when cholesterol 7α-hydroxylase activity is low. In cases with enhanced activity of cholesterol 7α-hydroxylase, the “neutral” pathway is connected to the “acidic” pathway via 7α,26-dihydroxy-4-cholesten-3-one, whereas a flow from the acidic pathway to cholic acid appears to be of minor importance.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 631-640"},"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)90182-R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366609","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":"The state transitions of normal and mutant androgen-receptor complexes in human genital skin fibroblasts","authors":"Morris Kaufman,&nbsp;Leonard Pinsky,&nbsp;Bruce Gottlieb,&nbsp;Mark Trifiro","doi":"10.1016/0022-4731(90)90184-T","DOIUrl":"10.1016/0022-4731(90)90184-T","url":null,"abstract":"<div><p>We have incubated cells from controls and subjects with receptor-defective androgen resistance with ³H-labelled testosterone (T), methyltrienolone (MT), dihydrotestos-terone (DHT) or mibolerone (MB) and studied the temperature dependance of the dissociation rate constants of these various androgen-receptor (A-R) complexes both within cells and after they were extracted from them. In control cells, Arrhenius plots for T-, MT-, DHT- and MB-R complexes were linear and formed a hierarchy of dissociation states with energies of state IV &gt; III &gt; II &gt; I, respectively. Relative to this hierarchy, the dissociation states of the MB-, DHT- and MT-R complexes in mutant cells were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. When extracted from cells control or mutant T- or MT-R complexes, and mutant (but not control) DHT- or MB-R complexes lowered their respective dissociation rates by undergoing state transitions in conformity with the hierarchy. Hence we propose that different A-R complexes reach different dissociative states by undergoing sequential transitions along a common pathway, and that these transitions are co-regulated both by the chemical characteristics of the bound androgen and by other cellular non-receptor factors.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 6","pages":"Pages 651-657"},"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)90184-T","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13366611","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}