TY  - JOUR
AB  - © 2017 Society for Endocrinology Printed in Great Britain.In an attempt to define novel genetic loci involved in the pathophysiology of primary aldosteronism, a mutagenesis screen after treatment with the alkylating agent N-ethyl-N-nitrosourea was established for the parameter aldosterone. One of the generated mouse lines with hyperaldosteronism was phenotypically and genetically characterized. This mouse line had high aldosterone levels but normal creatinine and urea values. The steroidogenic enzyme expression levels in the adrenal gland did not differ significantly among phenotypically affected and unaffected mice. Upon exome sequencing, point mutations were identified in seven candidate genes (Sspo, Dguok, Hoxaas2, Clstn3, Atm, Tipin and Mapk6). Subsequently, animals were stratified into wild-type and mutated groups according to their genotype for each of these candidate genes. A correlation of their genotypes with the respective aldosterone, aldosterone-to-renin ratio (ARR), urea and creatinine values as well as steroidogenic enzyme expression levels was performed. Aldosterone values were significantly higher in animals carrying mutations in four different genes (Sspo, Dguok, Hoxaas2 and Clstn3) and associated statistically significant adrenal Cyp11b2 overexpression as well as increased ARR was present only in mice with Sspo mutation. In contrast, mutations of the remaining candidate genes (Atm, Tipin and Mapk6) were associated with lower aldosterone values and lower Hsd3b6 expression levels. In summary, these data demonstrate association between the genes Sspo, Dguok, Hoxaas2 and Clstn3 and hyperaldosteronism. Final proofs for the causative nature of the mutations have to come from knock-out and knock-in experiments.
AU  - Perez-Rivas, L.G.*
AU  - Rhayem, Y.*
AU  - Sabrautzki, S.
AU  - Hantel, C.*
AU  - Rathkolb, B.
AU  - Hrabě de Angelis, M.
AU  - Reincke, M.*
AU  - Beuschlein, F.*
AU  - Spyroglou, A.*
C1  - 50138
C2  - 42202
CY  - Bristol
SP  - 67-68
TI  - Genetic characterization of a mouse line with primary aldosteronism.
JO  - J. Mol. Endocrinol.
VL  - 58
IS  - 2
PB  - Bioscientifica Ltd
PY  - 2017
SN  - 0952-5041
ER  - 

TY  - JOUR
AB  - Aldosterone is synthesized acutely from the zona glomerulosa cells upon stimulation by the renin-angiotensin-aldosterone system. Several enzymes are involved in this steroidogenic process including the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (Cyp11a1), and aldosterone synthase (Cyp11b2) which has been demonstrated to be transcriptionally regulated by the nuclear transcription factors NGF1-B and Nurr1. We investigated the short time transcriptional regulation of these genes in wild-type mice at 10 min intervals for 1 h following application of 0.2 nmol angiotensin II (ANGII) or sodium chloride in comparison sham injections. Using real-time PCR a fast upregulation of adrenal Cyp11b2 expression (53+/-5% increase over baseline) could be observed 10 min after sham injection which was accompanied by a transient increase in aldosterone secretion while StAR and Cyp11a1 upregulation was delayed and more sustained. ANGII caused an increase of StAR and Cyp11a1 expression similar to that observed after sham injection while Cyp11b2 upregulation was more pronounced (10 min, 236+/-39%) and reflected ANGII induced stimulation of aldosterone output. Sodium challenge was followed by a sustained reduction of all three genes examined (Cyp11b2, 20 min, -63+/-6%) which was accompanied by a significant suppression of aldosterone secretion detectable after 60 min. While increases in NGF1-B mRNA levels were similar between the treatment groups, Nurr1 expression levels were induced only upon ANGII administration. These data suggest that acute regulation of aldosterone synthesis is accompanied by fast transcriptional modulation of steroidogenic enzymes and transcription factors that are likely to be involved in aldosterone secretion.
AU  - Spyroglou, A.*
AU  - Manolopoulou, J.*
AU  - Wagner, S.
AU  - Bidlingmaier, M.*
AU  - Reincke, M.*
AU  - Beuschlein, F.*
C1  - 189
C2  - 26317
SP  - 407-413
TI  - Short term regulation of aldosterone secretion after stimulation and suppression experiments in mice.
JO  - J. Mol. Endocrinol.
VL  - 42
IS  - 5
PY  - 2009
SN  - 0952-5041
ER  - 

TY  - JOUR
AU  - Ohnesorg, T.*
AU  - Keller, B.
AU  - Hrabě de Angelis, M.
AU  - Adamski, J.
C1  - 4828
C2  - 23930
SP  - 185-197
TI  - Transcriptional regulation of human and murine 17β-hydroxysteroid dehydrogenase type-7 confers its participation in cholesterol biosynthesis.
JO  - J. Mol. Endocrinol.
VL  - 37
PY  - 2006
SN  - 0952-5041
ER  - 

TY  - JOUR
AU  - Mindnich, R.
AU  - Haller, F.
AU  - Halbach, F.
AU  - Möller, G.
AU  - Hrabě de Angelis, M.
AU  - Adamski, J.
C1  - 2074
C2  - 22931
SP  - 305-316
TI  - Androgen metabolism via 17β-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: Comparison of the human and the zebrafish enzyme.
JO  - J. Mol. Endocrinol.
VL  - 35
PY  - 2005
SN  - 0952-5041
ER  - 

TY  - JOUR
AU  - Santti, H.*
AU  - Mikkonen, L.*
AU  - Anand, A.*
AU  - Hirvonen-Santti, S.*
AU  - Toppari, J.*
AU  - Panhuysen, M.
AU  - Vauti, F.
AU  - Perera, M.*
AU  - Corte, G.*
AU  - Wurst, W.
AU  - Jänne, O.A.*
C1  - 1702
C2  - 22876
SP  - 645-654
TI  - Disruption of the murine PIASx gene results in reduced testis weight.
JO  - J. Mol. Endocrinol.
VL  - 34
PY  - 2005
SN  - 0952-5041
ER  - 

TY  - JOUR
AU  - de Launoit, Y.*
AU  - Adamski, J.
C1  - 21143
C2  - 19184
SP  - 227-240
TI  - Unique multifunctional HSD17B4 gene product: 17ß-hydroxysteroid dehydrogenase 4 and D-3- hydroxyacryl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome.
JO  - J. Mol. Endocrinol.
VL  - 22
PY  - 1999
SN  - 0952-5041
ER  - 

TY  - JOUR
AU  - Peltoketo, H.*
AU  - Luu-The, V.*
AU  - Simard, J.*
AU  - Adamski, J.
C1  - 21142
C2  - 19182
SP  - 1-11
TI  - 17ß-Hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family ; nomenclature and main characteristics of the 17HSD/KSR enzymes.
JO  - J. Mol. Endocrinol.
VL  - 23
PY  - 1999
SN  - 0952-5041
ER  -