TY  - JOUR
AU  - Adamski, J.
C1  - 73539
C2  - 57087
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
TI  - Facing challenges in modern steroid research.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 249
PB  - Pergamon-elsevier Science Ltd
PY  - 2025
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Adamski, J.
C1  - 75180
C2  - 57821
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
TI  - Obituary: Étienne-Émile Baulieu (1927-2025).
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 254
PB  - Pergamon-elsevier Science Ltd
PY  - 2025
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Penning, T.M.*
AU  - Adamski, J.
C1  - 74882
C2  - 57651
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
TI  - Frontiers in Steroid Research: Steroid Congress 2023.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 253
PB  - Pergamon-elsevier Science Ltd
PY  - 2025
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - 17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) catalyzes the conversion of highly active estrogens and androgens into their less active forms using NAD+ as cofactor. Substrate and cofactor specificities of 17β-HSD2 have been reported and potent 17β-HSD2 inhibitors have been discovered in a ligand-based approach. However, the molecular basis and the amino acids involved in the enzymatic functionality are poorly understood, as no crystal structure of the membrane-associated 17β-HSD2 exists. The functional properties of only few amino acids are known. The lack of topological information impedes structure-based drug design studies and limits the design of biochemical experiments. The aim of this work was the determination of the 17β-HSD2 topology. For this, the first homology model of 17β-HSD2 in complex with NAD+ and 17β-estradiol was built, using a multi-fragment “patchwork” approach. To confirm the quality of the model, fifteen selected amino acids were exchanged one by one using site directed mutagenesis. The mutants’ functional behavior demonstrated that the generated model was of very good quality and allowed the identification of several key amino acids involved in either ligand or internal structure stabilization. The final model is an optimal basis for further experiments like, for example, lead optimization.
AU  - Sager, C.P.*
AU  - Weber, S.
AU  - Negri, M.*
AU  - Banachowicz, P.
AU  - Möller, G.
AU  - Adamski, J.
AU  - Hartmann, R.W.*
AU  - Marchais-Oberwinkler, S.*
C1  - 60810
C2  - 49599
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
TI  - Homology modeling meets site-directed mutagenesis: An ideal combination to elucidate the topology of 17β-HSD2.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 206
PB  - Pergamon-elsevier Science Ltd
PY  - 2021
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - The African clawed frog, Xenopus laevis, is a versatile model for biomedical research and is largely similar to mammals in terms of organ development, anatomy, physiology, and hormonal signaling mechanisms. Steroid hormones control a variety of processes and their levels are regulated by hydroxysteroid dehydrogenases (HSDs). The subfamily of 20β-HSD type 2 enzymes currently comprises eight members from teleost fish and mammals. Here, we report the identification of three 20β-HSD type 2 genes in X. tropicalis and X. laevis and the functional characterization of the two homeologs from X. laevis. X. laevis Hsd20b2.L and Hsd20b2.S showed high sequence identity with known 20β-HSD type 2 enzymes and mapped to the two subgenomes of the allotetraploid frog genome. Both homeologs are expressed during embryonic development and in adult tissues, with strongest signals in liver, kidney, intestine, and skin. After recombinant expression in human cell lines, both enzymes co-localized with the endoplasmic reticulum and catalyzed the conversion of cortisone to 20β-dihydrocortisone. Both Hsd20b2.L and Hsd20b2.S catalyzed the 20β-reduction of further C21 steroids (17α-hydroxyprogesterone, progesterone, 11-deoxycortisol, 11-deoxycorticosterone), while only Hsd20b2.S was able to convert corticosterone and cortisol to their 20β-reduced metabolites. Estrone was only a poor and androstenedione no substrate for both enzymes. Our results demonstrate multispecificity of 20β-HSD type 2 enzymes from X. laevis similar to other teleost 20β-HSD type 2 enzymes. X. laevis 20β-HSD type 2 enzymes are probably involved in steroid catabolism and in the generation of pheromones for intraspecies communication. A role in oocyte maturation is unlikely.
AU  - Tokarz, J.
AU  - Schmitt, S.M.*
AU  - Möller, G.
AU  - Brändli, A.W.*
AU  - Adamski, J.
C1  - 61710
C2  - 50407
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
TI  - Functional characterization of two 20β-hydroxysteroid dehydrogenase type 2 homeologs from Xenopus laevis reveals multispecificity.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 210
PB  - Pergamon-elsevier Science Ltd
PY  - 2021
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Maternal smoking during pregnancy affects fetal neurological development. Metabolomic studies in the general population suggest that smoking is associated with characteristic metabolic alterations. We investigated the association between the maternal smoking status, the fetal metabolome and head circumference at birth, as a surrogate parameter of brain development. 320 mother/newborn pairs of the Berlin Birth Cohort were investigated. Anthropometric parameters, including head circumference, of newborns of smoking mothers, former smoking mothers, and never smoking mothers were compared to assess the impact of maternal smoking behavior. Associations between maternal smoking behavior and 163 cord blood metabolites and associations between newborn head circumference and concentrations of smoking behavior related metabolites were analysed. Male newborns of smoking mothers had a reduced head circumference when compared with newborns from former smoking and never smoking mothers (p < 0.05). Using linear regression models corrected for established confounding factors, maternal smoking during pregnancy showed an independent association with head circumference (95% CI: -0.75 similar to -0.41 cm, p = 2.45 x 10(-11)). In a stepwise linear regression model corrected for known confounding factors of brain growth lyso-phosphatidylcholine 20:3 (95% CI: 6.68 similar to 39.88 cm, p = 4.62 x 10(-4)) was associated with head circumference in male offspring only. None of the metabolites were associated with head circumference of female newborns. In conclusion, maternal smoking during pregnancy impacted on male offspring's development including brain development. The smoking related metabolite lysophosphatidylcholine 20:3 was associated with head circumference of male offspring.
AU  - Yong-Ping, L.*
AU  - Reichetzeder, C.*
AU  - Prehn, C.
AU  - Yin, L.H.*
AU  - Chu, C.*
AU  - Elitok, S.*
AU  - Krämer, B.K.*
AU  - Adamski, J.
AU  - Hocher, B.*
C1  - 58790
C2  - 48326
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
TI  - Impact of maternal smoking associated lyso-phosphatidylcholine 20:3 on offspring brain development.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 199
PB  - Pergamon-elsevier Science Ltd
PY  - 2020
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Rizner, T.L.*
AU  - Adamski, J.
C1  - 54650
C2  - 45720
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - 1-3
TI  - Paramount importance of sample quality in pre-clinical and clinical research-Need for standard operating procedures (SOPs).
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 186
PB  - Pergamon-elsevier Science Ltd
PY  - 2019
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Many enzymes from the short-chain dehydrogenase/reductase superfamily (SDR) have already been well characterized, particularly those that participate in crucial biochemical reactions in the human body (e.g. 11 beta-hydroxysteroid dehydrogenase 1, 17 beta-hydroxysteroid dehydrogenase 1 or carbonyl reductase 1). Several other SDR enzymes are completely or almost completely uncharacterized, such as DHRS1 (also known as SDR19C1). Based on our in silico and experimental approaches, DHRS1 is described as a likely monotopic protein that interacts with the membrane of the endoplasmic reticulum. The highest expression level of DHRS1 protein was observed in human liver and adrenals. The recombinant form of DHRS1 was purified using the detergent ndodecy1-beta-D-maltoside, and DHRS1 was proven to be an NADPH-dependent reductase that is able to catalyse the in vitro reductive conversion of some steroids (estrone, androstene-3,17-dione and cortisone), as well as other endogenous substances and xenobiotics. The expression pattern and enzyme activities fit to a role in steroid and/or xenobiotic metabolism; however, more research is needed to fully clarify the exact biological function of DHRS1.
AU  - Zemanová, L.*
AU  - Navrátilová, H.*
AU  - Andrýs, R.*
AU  - Šperková, K.*
AU  - Andrejs, J.*
AU  - Kozáková, K.*
AU  - Meier, M.
AU  - Möller, G.
AU  - Novotná, E.*
AU  - Šafr, M.*
AU  - Adamski, J.
AU  - Wsól, V.*
C1  - 53970
C2  - 45153
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - 80-89
TI  - Initial characterization of human DHRS1 (SDR19C1), a member of the short chain dehydrogenase/reductase superfamily.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 185
PB  - Pergamon-elsevier Science Ltd
PY  - 2019
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - In endometrial cancer, biomarkers for preoperative identification of patients with low risk for disease progression would enable stratification according to the extent of surgery needed, and would avoid the complications that can be associated with radical surgery. A panel of proteins, amino acids, enzymes, and miRNA has been investigated as potential biomarkers for endometrial cancer. At the time of the manuscript submission targeted metabolomics/lipidomics approaches have not been applied to biomarker research in endometrial cancer. Using electrospray ionization-tandem mass spectrometry we quantified 163 metabolites in 126 plasma samples (61 patients with endometrial cancer, 65 control patients). Three single phosphatidylcholines were identified with significantly decreased levels in patients with endometrial cancer. A diagnostic model was defined as the ratio between acylcamitine C16 and phosphatidylcholine PCae C40:1, the ratio between proline and tyrosine, and the ratio between the two phosphatidylcholines PCaa C42:0 and PCae C44:5; which provided sensitivity of 85.25%, specificity of 69.23%, and AUC of 0.837. Addition of smoking status further improved the constructed diagnostic model (AUC = 0.855). The presence of the major prognostic factors of deep myometrial invasion and lymphovascular invasion were also associated with altered metabolite concentrations. A prognostic model for deep myometrial invasion included the ratio between two hydroxysphingomyelins SMOH C14:1 and SMOH C24:1, and the ratio between two phosphatidylcholines PCaa C40:2 and PCaa C42:6, which provided sensitivity of 81.25%, specificity of 86.36%, and AUC of 0.857. The model for lymphovascular invasion included the ratio between two phosphatidylcholines PCaa C34:4 and PCae C38:3, and the ratio between acylcarnitine C16:2 and phosphatidylcholine PCaa C38:1, which provided sensitivity of 88.89%, specificity of 84.31%, and AUC of 0.935.
AU  - Knific, T.*
AU  - Vouk, K.*
AU  - Smrkolj,*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - Rižner, T.L.*
C1  - 52775
C2  - 44349
CY  - Oxford
SP  - 312-321
TI  - Models including plasma levels of sphingomyelins and phosphatidylcholines as diagnostic and prognostic biomarkers of endometrial cancer.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 178
PB  - Pergamon-elsevier Science Ltd
PY  - 2018
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Rizner, T.L.*
AU  - Adamski, J.
C1  - 52660
C2  - 44229
SP  - 1-3
TI  - It is high time to discontinue use of misidentified and contaminated cells: Guidelines for description and authentication of cell lines.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 182
PY  - 2018
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Metformin is the most important first-line treatment for type 2 diabetes mellitus (T2DM) but its exact mode of action remains unknown. In this study, we used targeted metabolomics to gain new insights into the metabolic effects of metformin in humans with T2DM. We also examined changes in the serum steroid hormone profile. We quantified 167 serum metabolites and 19 steroid hormones using liquid chromatography-tandem mass spectrometry at three time points in individuals with previously untreated T2DM: before the start of metformin therapy (time point A), after the first dose (B) and after short-term therapy for 4-6 weeks (C). For metabolite analysis, we split the study cohort into a discovery and a replication study of 88 and 45 subjects, respectively. The statistical analysis was done using linear mixed-effects models. Among the metabolites quantified, citrulline showed the most pronounced changes. Compared to its baseline serum concentration, citrulline was reduced by 17% after the first dose of metformin (p=1.34E-07) and by 24% after short-term therapy (p=2.84E-08) in the discovery study. These results were confirmed in the replication study. The only other metabolite significantly changed after correction for multiple testing was PC ae C36:4 between baseline and 4-6 weeks. The serum steroid hormone profile showed no significant changes after metformin intake. In summary, we observed an immediate and sustained reduction of serum citrulline by metformin in humans. This may be relevant for some of the wanted or unwanted effects of the drug.
AU  - Breier, M.
AU  - Wahl, S.
AU  - Prehn, C.
AU  - Ferrari, U.
AU  - Sacco, V.
AU  - Weise, M.
AU  - Grallert, H.
AU  - Adamski, J.
AU  - Lechner, A.
C1  - 51716
C2  - 43469
CY  - Oxford
SP  - 114-119
TI  - Immediate reduction of serum citrulline but no change of steroid profile after initiation of metformin in individuals with type 2 diabetes.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 174
PB  - Pergamon-elsevier Science Ltd
PY  - 2017
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Rizner, T.L.*
AU  - Sasano, H.*
AU  - Choi, M.H.*
AU  - Odermatt, A.*
AU  - Adamski, J.
C1  - 47541
C2  - 40649
CY  - Oxford
SP  - 40-42
TI  - Recommendations for description and validation for antibodies for research use.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 156
PB  - Pergamon-elsevier Science Ltd
PY  - 2016
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Endometriosis is a complex, polygenic, and estrogen-dependent disease that affects 6% to 10% of women of reproductive age, and 30% to 50% of women with infertility and/or pelvic pain. Surgical diagnosis of endometriosis is still the gold standard, as there are currently no diagnostic biomarkers available. Due to the invasive diagnostics, it can take up to 11 years before affected women are diagnosed and receive the appropriate treatment. We performed a targeted metabolomics study to search for potential semi-invasive biomarkers in peritoneal fluid from endometriosis patients. Our case-control study comprised 29 ovarian endometriosis patients and 36 healthy control women. The 148 metabolites included acylcarnitines, glycerophospholipids, and sphingolipids, which were quantified by electrospray ionization tandem mass spectrometry. The strength of association between the metabolites and the metabolite ratios and disease was assessed using crude and adjusted odds ratios. The best combination of biomarkers was then selected by performing step-wise logistic regression. Our analysis reveals significantly decreased concentrations of 10 metabolites, of carnitine and acylcarnitines (C0, C8:1, C6/C4:1 DC, C10:1), phosphatidylcholines (PC aa C38:3, PC aa C38:4, PC aa C40:4, PC aa C40:5), and sphingomyelins (SM C16:1, SM C18:1), and 125 significantly altered metabolite ratios in patients versus control women. The best model includes two ratios: a carnitine to a phosphatidylcholine (C0/PC ae C36:0); and between two phosphatidylcholines (PC aa C30:0/PC ae C32:2). When adjusted for age, this provides sensitivity of 82.8% and specificity of 94.4%, with AUC of 0.944. Our study supports the importance of carnitine, phospatidylcholine, and sphingomyelin metabolites in the pathophysiology of endometriosis, and confirms the potential for the combination of individual metabolite ratios to provide biomarkers for semi-invasive diagnostics.
AU  - Vouk, K.*
AU  - Ribič-Pucelj, M.*
AU  - Adamski, J.
AU  - Rizner, T.L.*
C1  - 47989
C2  - 39799
CY  - Oxford
SP  - 60-69
TI  - Altered levels of acylcarnitines, phosphatidylcholines, and sphingomyelins in peritoneal fluid from ovarian endometriosis patients.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 159
PB  - Pergamon-elsevier Science Ltd
PY  - 2016
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Adamski, J.
C1  - 46447
C2  - 37540
SP  - 1-2
TI  - Perspectives in steroid research.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 153
PY  - 2015
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Adamski, J.
C1  - 27179
C2  - 32566
SP  - 1-2
TI  - 2nd congress on steroid research.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 137
PB  - Pergamon-Elsevier Science
PY  - 2013
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Zebrafish, Danio rerio, has long been used as a model organism in developmental biology. Nowadays, due to their advantages compared to other model animals, the fish gain popularity and are also increasingly used in endocrinology. This review focuses on an important aspect of endocrinology in zebrafish by summarizing the progress in steroid hormone related research. We present the state of the art of research on steroidogenesis, the action of steroid hormones, and steroid catabolism and cover the incremental usage of zebrafish as a test animal in endocrine disruption research. By this approach, we demonstrate that some aspects of steroid hormone research are well characterized (e.g., expression patterns of the genes involved), while other aspects such as functional analyses of enzymes, steroid hormone elimination, or the impact of steroid hormones on embryonic development or sex differentiation have not been extensively studied and are poorly understood.
AU  - Tokarz, J.
AU  - Möller, G.
AU  - Hrabě de Angelis, M.
AU  - Adamski, J.
C1  - 24318
C2  - 31526
SP  - 165-173
TI  - Zebrafish and steroids: What do we know and what do we need to know?
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 137
PB  - Pergamon-Elsevier
PY  - 2013
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - 17β-Hydroxysteroid dehydrogenases (17β-HSDs) are oxidoreductases, which play a key role in estrogen and androgen steroid metabolism by catalyzing final steps of the steroid biosynthesis. Up to now, 14 different subtypes have been identified in mammals, which catalyze NAD(P)H or NAD(P)(+) dependent reductions/oxidations at the 17-position of the steroid. Depending on their reductive or oxidative activities, they modulate the intracellular concentration of inactive and active steroids. As the genomic mechanism of steroid action involves binding to a steroid nuclear receptor, 17β-HSDs act like pre-receptor molecular switches. 17β-HSDs are thus key enzymes implicated in the different functions of the reproductive tissues in both males and females. The crucial role of estrogens and androgens in the genesis and development of hormone dependent diseases is well recognized. Considering the pivotal role of 17β-HSDs in steroid hormone modulation and their substrate specificity, these proteins are promising therapeutic targets for diseases like breast cancer, endometriosis, osteoporosis, and prostate cancer. The selective inhibition of the concerned enzymes might provide an effective treatment and a good alternative to the existing endocrine therapies. Herein, we give an overview of functional and structural aspects for the different 17β-HSDs. We focus on steroidal and non-steroidal inhibitors recently published for each subtype and report on existing animal models for the different 17β-HSDs and the respective diseases. Article from the Special issue on Targeted Inhibitors.
AU  - Marchais-Oberwinkler, S.*
AU  - Henn, C.*
AU  - Möller, G.
AU  - Klein, T.*
AU  - Negri, M.*
AU  - Oster, A.*
AU  - Spadaro, A.*
AU  - Werth, R.*
AU  - Wetzel, M.*
AU  - Xu, K.*
AU  - Frotscher, M.*
AU  - Hartmann, R.W.*
AU  - Adamski, J.
C1  - 6462
C2  - 28738
CY  - Oxford
SP  - 66-82
TI  - 17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: Protein structures, functions, and recent progress in inhibitor development.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 125
IS  - 1-2
PB  - Pergamon-Elsevier
PY  - 2011
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - no Abstract
AU  - Penning, T.M.*
AU  - Adamski, J.
C1  - 6696
C2  - 29133
SP  - e1-e4
TI  - Integration of steroid research: Perspectives on environment factors, homeostasis in health, and disease treatment.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 126
PB  - Elsevier
PY  - 2011
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - 17β-Hydroxysteroid dehydrogenase type 3 and 5 (17β-HSD3 and 17β-HSD5) catalyze testosterone biosynthesis and thereby constitute therapeutic targets for androgen-related diseases or endocrine-disrupting chemicals. As a fast and efficient tool to identify potential ligands for 17βHSD3/5, ligand- and structure-based pharmacophore models for both enzymes were developed. The models were evaluated first by in silico screening of commercial compound databases and further experimentally validated by enzymatic efficacy tests of selected virtual hits. Among the 35 tested compounds, 11 novel inhibitors with distinct chemical scaffolds, e.g. sulfonamides and triazoles, and with different selectivity properties were discovered. Thereby, we provide several potential starting points for further 17β-HSD3 and 17β-HSD5 inhibitor development. Article from the Special issue on Targeted Inhibitors.
AU  - Schuster, D.*
AU  - Kowalik, D.
AU  - Kirchmair, J.*
AU  - Laggner, C.*
AU  - Markt, P.*
AU  - Aebischer-Gumy, C.*
AU  - Ströhle, F.
AU  - Möller, G.
AU  - Wolber, G.*
AU  - Wilckens, T.*
AU  - Langer, T.*
AU  - Odermatt, A.*
AU  - Adamski, J.
C1  - 6463
C2  - 28739
CY  - Oxford
SP  - 148-161
TI  - Identification of chemically diverse, novel inhibitors of 17β-hydroxysteroid dehydrogenase type 3 and 5 by pharmacophore-based virtual screening.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 125
IS  - 1-2
PB  - Pergamon-Elsevier
PY  - 2011
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - In the search for novel biomarkers of endometriosis, we selected 152 genes from the GeneLogic database based on results of genome-wide expression analysis of ovarian endometriosis, plus 20 genes related to estrogen metabolism and action. We then performed low-density array analysis of these 172 genes on 11 ovarian endometriosis samples and 9 control endometrium samples. Principal component analysis of the gene expression levels showed clear separation between the endometriosis and control groups. We identified 78 genes as differentially expressed. Based on Ingenuity pathway analysis, these differentially expressed genes were arranged into groups according to biological function. These analyses revealed that 32 differentially expressed genes are estrogen related, 23 of which have not been reported previously in connection with endometriosis. Functional annotation showed that 25 and 22 genes are associated with the biological terms "secreted" and "extracellular region", respectively. Differential expression of 4 out of 5 genes related to estrogen metabolism and action (ESR1, ESR2, PGR and BGN) was also confirmed by immunohistochemistry. Our study thus reveals differential expression of several genes that have not previously been associated with endometriosis and that encode potential novel biomarkers and drug targets.
AU  - Vouk, K.*
AU  - Smuc, T.*
AU  - Guggenberger, C.
AU  - Ribič-Pucelj, M.*
AU  - Sinkovec, J.*
AU  - Husen, B.*
AU  - Thole, H.*
AU  - Houba, P.*
AU  - Thaete, C.*
AU  - Adamski, J.
AU  - Rizner, T.L.*
C1  - 6747
C2  - 29203
CY  - Oxford, UK
SP  - 231-242
TI  - Novel estrogen-related genes and potential biomarkers of ovarian endometriosis identified by differential expression analysis.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 125
IS  - 3-5
PB  - Pergamon Press
PY  - 2011
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - no Abstract
AU  - Ceglarek, U.*
AU  - Shackleton, C.*
AU  - Stanczyk, F.Z.*
AU  - Adamski, J.
C1  - 5959
C2  - 28356
SP  - 479-480
TI  - Steroid profiling and analytics: Going towards sterome.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 121
IS  - 3-5
PB  - Elsevier
PY  - 2010
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - While 25-OH-D3 serum levels in humans undergo a large seasonal variation, 1,25-(OH)2-D3 is regulated within a narrow range. We speculate that in addition to the known genomic and nongenomic regulation there could be further epigenetic mechanisms involved. We annotated the human CYP27B1 (alpha-1-hydroxylase) and CYP24A1 (24-hydroxylase) genes for CpG islands and sequenced these in bisulfite treated DNA extracted of peripheral blood lymphocytes from 384 individuals. 40 CpG sites could be analyzed, of these 15 in CYP27B1 and 25 in CYP24A1. The average methylation ratio (MR) in CYP27B1 was 11% (s.d. 5%) with the highest ratio observed in exon 1 (38%). CYP24A1 showed only a 6.5% MR (s.d. 5%). Neither CYP24A1 nor CYP27B1 MR correlated with season of examination date nor with current 25-OH-D3 and 1,25-(OH)2-D3 serum levels except of a weak association of three consecutive CYP27B1 CpG sites and 25-OH-D3 levels. In summary, human PBLs showed only weak methylation in the upstream region of CYP27B1 and none in CYP24A1. As PBLs represent an heterogeneous pool of cells, a further analysis of the seasonal methylation pattern in B or T cell subsets (or other tissues like liver or kidney) is warranted including an extended coverage of the CYP27B1 promotor.
AU  - Wjst, M.
AU  - Heimbeck, I.
AU  - Kutschke, D.
AU  - Pukelsheim, K.
C1  - 5261
C2  - 27874
SP  - 80-83
TI  - Epigenetic regulation of vitamin D converting enzymes.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 121
IS  - 1-2
PB  - Elsevier
PY  - 2010
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Adamski, J.
C1  - 1353
C2  - 26659
SP  - 1-2
TI  - Mission to steroids.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 113
IS  - 1-2
PB  - Pergamon, Elsevier Science
PY  - 2009
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - The protein superfamily of short-chain dehydrogenases/reductases (SDRs) today comprises over 20,000 members found in pro- and eukaryotes. Despite low amino acid sequence identity (only 15-30%), they share several similar characteristics in conformational structures, the N-terminal cofactor (NAD(P)/NAD(P)H) binding region being the most conserved. The enzymes catalyze oxido-reductive reactions and have a broad spectrum of substrates. Not all recently identified SDRs have been analyzed in detail yet, and we therefore characterized two rudimentarily annotated human SDR candidates: an orphan SDR (SDR-O) and hydroxysteroid dehydrogenase like 2 (HSDL2). We analyzed the amino acid sequence for cofactor preference, performed subcellular localization studies, and a screening for substrates of the enzymes, including steroid hormones and retinoids. None of both tested proteins showed a significant conversion of steroid hormones. However, the peroxisomal localization of human HSDL2 may suggest an involvement in fatty acid metabolism. For SDR-O a weak conversion of retinal into retinol was detectable in the presence of the cofactor NADH.
AU  - Kowalik, D.
AU  - Haller, F.
AU  - Adamski, J.
AU  - Möller, G.
C1  - 552
C2  - 26984
SP  - 117-124
TI  - In search for function of two human orphan SDR enzymes: Hydroxysteroid dehydrogenase like 2 (HSDL2) and short-chain degydrogenase/reductase-orphan (SDR-O).
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 117
IS  - 4-5
PB  - Pergamon-Elsevier Science Ltd
PY  - 2009
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - The enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has become an important drug target for breast cancer because it catalyzes the interconversion of estrone to the biologically more potent estradiol which also plays a crucial role in the etiology of breast cancer. Patients with an increased expression of the 17beta-HSD1 gene have a significantly worse outcome than patients without. Inhibitors for 17beta-HSD1 are therefore included in therapy development. Here we have studied binding of 17beta-HSD1 to substrates and a number of inhibitors using NMR spectroscopy. Ligand observed NMR spectra show a strong pH dependence for the phytoestrogens luteolin and apigenin but not for the natural ligands estradiol and estrone. Moreover, NMR competition experiments show that the phytoestrogens do not replace the estrogens despite their similar inhibition levels in the in vitro assay. These results strongly support an additional 17beta-HSD1 binding site for phytoestrogens which is neither the substrate nor the co-factor binding site. Docking experiments suggest the dimer interface as a possible location. An additional binding site for the phytoestrogens may open new opportunities for the design of inhibitors, not only for 17beta-HSD1, but also for other family members of the short chain dehydrogenases.
AU  - Michiels, P.J.*
AU  - Ludwig, C.*
AU  - Stephans, M.*
AU  - Fischer, C.*
AU  - Möller, G.
AU  - Adamski, J.
AU  - Messinger, J.*
AU  - van Dongen, M.*
AU  - Thole, H.*
AU  - Günther, U.L.*
C1  - 1977
C2  - 26800
SP  - 93-98
TI  - Ligand-based NMR spectra demonstrate an additional phytoestrogen binding site for 17β-hydroxysteroid dehydrogenase type 1.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 117
IS  - 4-5
PY  - 2009
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - The metabolism of steroids at position 17 is catalysed by a growing number of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs). Several human diseases like breast or prostate cancer, endometriosis, metabolic syndrome and mental diseases were associated
AU  - Prehn, C.
AU  - Möller, G.
AU  - Adamski, J.
C1  - 1108
C2  - 26660
CY  - Oxford
SP  - 72-77
TI  - Recent advances in 17β-hydroxysteroid dehydrogenases.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 114
IS  - 1-2
PB  - Pergamon-Elsevier Science Ltd
PY  - 2009
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Inborn errors of cholesterol biosynthesis caused by dysfunctionality of single enzymes are known to cause severe malformation syndromes like X-linked chondrodysplasia punctata (CDPX2), CHILD syndrome or Smith-Lemli-Opitz-syndrome (SLOS). In this study we established the method of RNA interference (RNAi) for analyzing the molecular mechanisms underlying disrupted cholesterol biosynthesis. For different genes involved in the cholesterol biosynthesis pathway-NAD(P) dependent steroid dehydrogenase-like (NSDHL), 17-beta hydroxysteroid dehydrogenase type 7 (HSD17B7) and emopamil binding protein (EBP)-shRNA sequences were designed and tested for their effectiveness. For a better comparability of the experiments and to avoid different transfection efficiencies, examined shRNA sequences which reached a knock down of at least 80% were stably transfected in a HeLa cell line with a tetracycline-regulated expression (HeLa T-REx). These stable transfected cell lines represent novel tools for the analysis of cholesterol biosynthesis.
AU  - Guggenberger, C.
AU  - Ilgen, D.
AU  - Adamski, J.
C1  - 607
C2  - 24876
SP  - 105-109
TI  - Functional analysis of cholesterol biosynthesis by RNA interference.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 104
IS  - 3-5
PB  - Elsevier
PY  - 2007
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Three retinol dehydrogenases (RDHs) were tested for steroid converting abilities: human and murine RDH 12 and human RDH13. RDH12 is involved in retinal degeneration in Leber's congenital amaurosis (LCA). We show that murine Rdh12 and human RDH13 do not reveal activity towards the checked steroids, but that human type 12 RDH reduces dihydrotestosterone to androstanediol, and is thus also involved in steroid metabolism. Furthermore, we analyzed both expression and subcellular localization of these enzymes.
AU  - Keller, B.
AU  - Adamski, J.
C1  - 4860
C2  - 24473
SP  - 190-194
TI  - RDH12, a retinol dehydrogenase causing Leber's congenital amaurosis, is also involved in steroid metabolism.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 104
IS  - 3-5
PB  - Elsevier
PY  - 2007
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Among the family of 17beta-hydroxysteroid dehydrogenases, the type 2 (17beta-HSD 2) is the main enzyme responsible for inactivation of estrogens and androgens, catalyzing the oxidation of the C17 hydroxyl group. 17beta-HSD 2 has been studied only in mammals, its occurrence and function in other vertebrates hardly known. We investigated the presence of homologs in non-mammalian species and found sequences of 17beta-HSD 2 and its closest homolog 11beta-HSD 2 in zebrafish (Danio rerio), Takifugu rubripes, Tetraodon nigroviridis, Xenopus tropicalis and chicken databases. Furthermore, we cloned zebrafish 17beta-HSD 2 from ovarian tissue and found high expression also in the testis of adult fish and throughout embryogenesis. The enzyme, though, is inactive likely due to a non-sense N-terminal region including a dysfunctional cofactor binding motif. Replacement of the affected part by the corresponding human 17beta-HSD 2 sequence fully restored enzymatic activity. Comparison of all retrieved 17beta-HSD 2 sequences indicates that this functional loss may have occurred only in zebrafish, where steroid inactivation at position C17 seems to pursue without the protein studied. The closely related 11beta-HSD 2 is unlikely to substitute for 17beta-HSD 2 since in our hands it did not catalyze the respective oxidation of testosterone or estradiol.
AU  - Mindnich, R.
AU  - Hrabě de Angelis, M.
AU  - Adamski, J.
C1  - 3401
C2  - 24474
SP  - 35-43
TI  - Functional genome analysis indicates loss of 17beta-hydroxysteroid dehydrogenase type 2 enzyme in the zebrafish.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 103
IS  - 1
PB  - Elsevier
PY  - 2007
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - Determining the functional aspects of a gene or protein is a difficult and time-consuming process. De novo analysis is surely the hardest and so it is often quite useful to start with a comparison to functionally or structurally related proteins. Although 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD 1) can hardly be called a new protein but rather the best characterized among the family of 17beta-HSDs some aspects of structure–function relationships remain unclear. We have sought new aspects of 17beta-HSD 1 function through a comparison with its closest homolog, a photoreceptor-associated retinol dehydrogenase (prRDH). Overall amino acid identity and size of the proteins are highly conserved, but major differences occur in the C-termini, where prRDH, but not 17beta-HSD 1, harbors motifs indicative of membrane localization. To gain insight into substrate discrimination by prRDH and 17beta-HSD 1, we constructed 3D-structure models of the corresponding zebrafish enzymes. Investigation of the substrate binding site revealed a few identical amino acids, and suggested a role for G143 in zebrafish 17beta-HSD 1 and M146 and M147 in the two zebrafish paralogs prRDH 1 and prRDH 2, respectively, in substrate specificity. Activity measurements of modified proteins in transiently transfected intact HEK 293 cells hint at a putative role of these amino acids in discrimination between steroid and retinoid substrates.
AU  - Mindnich, R.
AU  - Adamski, J.
C1  - 4859
C2  - 24472
SP  - 334-339
TI  - Functional aspects of 17beta-hydroxysteroid dehydrogenase 1 determined by comparison to a closely related retinol dehydrogenase.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 104
IS  - 3-5
PB  - Elsevier
PY  - 2007
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - To identify genome regions linked to serum vitamin D metabolites we analyzed 25-OH-D3 and 1,25-(OH)2-D3 levels from 947 participants of a family study recruited for asthma.From these individuals data were available from a previous genome scan that included 364 autosomal microsatellite marker. 25-OH-D3 levels showed a heritability of 80% in these families while 1,25-(OH)2-D3 reached only 30%. Genome-wide linkage using variance component analysis showed increased LOD scores for 25-OH-D3 at marker D1S2815 (unadjusted LOD 2.9), D2S2153 (LOD 3.4), D5S2017 (LOD 2.5), D6S260 (LOD 2.1) and D17S1824 (2.5). In contrast, the maximum LOD score for 1,25-(OH)2-D3 level was only 1.2 at marker D17S926.We conclude that only 25-OH-D3 serum levels are under genetic control where several genes are involved. The lead linkage region does not code for enzymes already known in the metabolic pathway of vitamin D and may therefore contain further genes relevant to the regulation of vitamin D serum levels.
AU  - Wjst, M.
AU  - Altmüller, J.
AU  - Braig, C.
AU  - Bahnweg, M.
AU  - André, E.
C1  - 5878
C2  - 24502
SP  - 799-802
TI  - A genome-wide linkage scan for 25-OH-D3 and 1,25-(OH)2-D3 serum levels in asthma families.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 103
IS  - 3-5
PB  - Elsevier
PY  - 2007
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Deluca, D.
AU  - Krazeisen, A.
AU  - Breitling, R.*
AU  - Prehn, C.
AU  - Möller, G.
AU  - Adamski, J.
C1  - 167
C2  - 22933
SP  - 285-292
TI  - Inhibition of 17beta-hydroxysteroid dehydrogenases by phytoestrogens: Comparison with other steroid metabolizing enzymes.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 93
PY  - 2005
SN  - 0960-0760
ER  - 

TY  - JOUR
AU  - Ohnesorg, T.
AU  - Adamski, J.
C1  - 2304
C2  - 22934
SP  - 259-261
TI  - Promoter analysis of human and mouse 17beta-hydroxysteroid dehydrogenase type 7.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 94
PY  - 2005
SN  - 0960-0760
ER  - 

TY  - JOUR
AB  - We studied the influence of the antiprogestin onapristone (ZK 98.299) and the progestin medroxyprogesterone acetate (MPA) on the proliferation and hormone receptor levels of the following human breast cancer cell lines: the oestrogen receptor (ER) and progesterone receptor (PR) negative cell line MDA-MB-231 and the ER- and PR-positive cell lines T47-D and SK-BR-3. MPA and onapristone both bind to the cellular PR and can inhibit the proliferation of hormone-dependent cells; PR-negative MDA-MB-231 cells are not inhibited. The growth inhibition of the ER- and PR-positive tumour cells induced by onapristone is accompanied by a significant accumulation of cells in the G0/G1 phase and a reduction of S-phase cells, while MPA does not change the distribution of the cell cycle phases. However, MPA reduces the cellular ER content by 27% and the PR content by more than 80%. Conversely, onapristone does not significantly affect ER and PR levels. The extent of growth inhibition by both drugs differs considerably: onapristone inhibits growth of both receptor positive cell lines (T47-D:39%; SK-BR-3:17%), while MPA affected growth in only SK-BR-3 (61%). These results indicate that even though the two drugs act through the PR, the inhibitory effect on the three cell lines of MPA may depend on ER concentration and its down-regulation, while the inhibitory effect of onapristone is mainly correlated to the PR concentration without significantly affecting ER levels. Since tumour cells with low ER concentration are growth suppressed by onapristone, but not by MPA, it remains to be examined whether antiprogestins should preferably be used in PR-positive tumours with a low ER concentration.
AU  - Classen, S.
AU  - Possinger, K.W.
AU  - Pelka-Fleischer, R.*
AU  - Wilmanns, W.
C1  - 40376
C2  - 40092
SP  - 315-319
TI  - Effect of onapristone and medroxyprogesterone acetate on the proliferation and hormone receptor concentration of human breast cancer cells.
JO  - J. Steroid Biochem. Mol. Biol.
VL  - 45
IS  - 4
PY  - 1993
SN  - 0960-0760
ER  -