Searchable abstracts of presentations at key conferences in endocrinology

ea0029p91 | Adrenal cortex | ICEECE2012

Low SLC26A2 expression in adrenal cells is associated with high aldosterone output

Bozoglu T. , Spyroglou A. , Reincke M. , Beuschlein F.

A genome-wide association study indicated a correlation between a locus at 5q32 and high aldosterone to renin ratio in subjects from KORA F4 survey. As we considered the genes in this locus for their potential relevance for the etiology of primary aldosteronism, we observed significantly higher expression of one of them, SLC26A2, in mouse adrenal glands, even though the gene’s function in the adrenal was not reported in the literature. Using the human adrenocortical cell ...

ea0026oc5.2 | Hormone metabolism and action | ECE2011

Site specific overexpression of urocortin 2 results in modulation of steroidogenesis in vivo

Spyroglou A , Hill A , Mueller-Peltzer K , Deussing J , Beuschlein F

Urocortin 2 (Ucn2) is a recently identified neuropeptide of the CRF-Family, involved in homeostatic mechanisms for stress response and control of anxiety. To further elucidate Ucn2 effects on steroidogenesis, we developed a mouse model with Ucn2 overexpression in the adrenals, gonads and parts of the hypothalamus, by crossbreeding SF1-Cre+/− mice with R26stop UCN2/stop UCN2 mice. Following genotypes were obtained: SF1-Cre&...

ea0026p3 | Adrenal cortex | ECE2011

MicroRNAs as endogenous modulators of glucocorticoid receptor expression in the adrenal gland after ACTH stimulation test

Hill A , Issler O , Spyroglou A , Haramati S , Chen A , Beuschlein F

MicroRNAs (miRs) are a subset of small RNA molecules that regulate gene expression post-transcriptionally. Little is known about the expression and the role of miRs in the adrenal gland. Thus, we determined the miRs expression pattern under baseline conditions and 10, 30 and 60 min after ACTH stimulation test in mice adrenal glands using miRs microarray. The miRs expression profile of adrenals obtained from the array was bioinformatically analyzed to indentify miRs that putati...

ea0026p61 | Endocrine tumours and neoplasia | ECE2011

Liposome based strategies for the treatment of adrenocortical carcinoma

Hantel C , Lewrick F , Reincke M , Suss R , Beuschlein F

Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane. Recently we have developed a novel therapeutic approach by coupling a monoclonal IGF1 receptor blocking antibody (1H7) to sterically stabilized liposomal doxorubicin (SSLD). 1H7 coupled liposomes showed in vitro high and significant cellular association and furthermore internalization in various human tumor cell lines as well a...

ea0029s48.3 | Pathogenesis of primary aldosteronism | ICEECE2012

Potassium channels in primary aldosteronism

Warth R. , Bandulik S. , Penton D. , Tauber P. , Zennaro M. , Mulatero P. , Beuschlein F. , Barhanin J.

Potassium channels regulate the membrane voltage of aldosterone-producing glomerulosa cells in the adrenal glands. They are required for the unique K+ sensitivity of these cells and are targets of angiotensin II signaling. Several K+ channels show high levels of expression in the adrenal cortex and are believed to be important for the control of hormone secretion, e.g. KCNJ5, TASK1, TASK3, KCNMA1, and KCNQ1.In a pioneering study, Li...

ea0029p1 | Adrenal cortex | ICEECE2012

Targeting mutated β-catenin in vitro and in vivo inhibits cell proliferation and stimulates apoptosis: a promising therapeutic target in adrenocortical carcinoma

Ragazzon B. , Gaujoux S. , Hantel C. , Tissier F. , Rizk-Rabin M. , Beuschlein F. , Bertherat J.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic option. Activating β-catenin somatic mutations are observed in ACC and associated with a poor outcome. Activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might be a promising therapeutic target. The H295 cell line derived from an ACC harbors an activating β-catenin mutation. We herein assess the in vi...

ea0029p44 | Adrenal cortex | ICEECE2012

Female patients with primary aldosteronism are diagnosed earlier and have a better outcome

Pallauf A. , Fischer E. , Endres S. , Bidlingmaier M. , Beuschlein F. , Reincke M.

Introduction: Primary aldosteronism (PA) is the most frequent curable form of hypertension. Hypokalemia is a late symptom of PA. Consequently, PA often is not diagnosed for many years. Our aim was to identify clinical and laboratory parameters in a large cohort of PA patients obtained during their first assessment.Methods: 96 consecutive patients prospectively studied since 2008 at the German Conn’s Registry Center in Munich were eligible for this s...

ea0029p815 | Endocrine tumours and neoplasia | ICEECE2012

Differential TNFα -synthesis and signaling in endocrine tumors after treatment with the Tumor-Vascular-Disrupting Agent ASA404 (vadimezan)

Hantel C. , Ozimek A. , Frantsev R. , Scheller F. , Reincke M. , Mussack T. , Beuschlein F.

Recently, we investigated effects of the Tumor-VDA ASA404 in tumor models for neuroendocrine tumors of the gastroenteropancreatic system and adrenocortical carcinoma 24 hours after treatment of BON and NCIh295 tumor bearing mice with ASA404 (A), paclitaxel (P) or the combination (A+P). We detected for BON tumors extensive necrotic areas as well as a significant decrease in cell proliferation, increase of apoptotic cells and reduction of microvessels after A or A+P treatment wh...

ea0026p60 | Endocrine tumours and neoplasia | ECE2011

Development and characterisation of patient-individual tumor models for endocrine tumors

Hantel C , Scheller F , Ozimek A , Chiapponi C , Mussack T , Beuschlein F

Only a few cell lines are available for endocrine tumors which furthermore do not reflect heterogenous functional properties and specific therapeutic response rates of individual tumors. To facilitate patient individual treatments and thereby to optimize therapeutic efficacy, we are aiming at the development and characterisation of patient-individual tumor models. Pieces of surgical tumor specimen from four adrenocortical carcinomas, one aldosterone producing adenoma, one pheo...

ea0011oc11 | Steroids and reproductive endocrinology | ECE2006

The adrenal X-zone is involved in progesterone inactivation

Beuschlein F , Heshkovitz L , Klammer S , Lichtenauer U , Shapiro I , Krup M , Weinstein Y

20alpha-hydroxysteroid dehydrogenase (20αHSD) has been initially characterized as a progesterone metabolizing enzyme of the ovary mandatory for the final reduction of progesterone blood levels before parturition. As the exact zonal distribution and regulation of adrenal 20αHSD has not been defined, adrenal 20αHSD expression and activity was determined by western blotting, immunohistochemistry and enzymatic assays in wild type BALB/c mice of both genders at diffe...