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Partner 20 - Institute of Experimental Endocrinology Slovak Academy of Sciences

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Link to group leader's CV.

University and research group information

The Institute of Experimental Endocrinology of the Slovak Academy of Sciences was established on December 1, 1951, with nationwide research activity in Slovakia. This Institute was a divisional institution of the Slovak Ministry of Health.

 

The main tasks of the Institute included: (a) organization, coordination and materialization of basic and clinical endocrinological research, (b) organization and materialization of regional survey of diseases of the endocrine system, in light of the project of the Ministry of Health, (c) the design of working plans to promote health conditions of the population in Slovakia and supervision of measures aiming at improvement of the health status of the population concerning prevention and reduction of the incidence of endocrine disorders, (d) organization, coordination and expert supervision of individual endocrinological care provided by thyroid disorders and other endocrinopathy clinics, (e) training of personnel for field investigation and surveillance of health control measures.

 

Research activities of the Institute have ever more been focused on elucidation of processes involved in the effect of hormones in the integrated organism and at cellular level, with the aim to detect derangements leading to serious diseases. Investigation concerns factors affecting the response of the body to stress stimuli, particularly processes of neuroendocrine regulation, the role of neurotransmitters and neuropeptides, involved in the response of the body to stressors.

 

A further field of interest relates to the effect of nutrition and of genetic factors on the response of tissues to hormones, on humoral regulation of lipid metabolism, and on the role of nutrition, and especially of lipid intake, in the development of metabolic defects, including insulin resistance. Studies dealing with processes of biologically active peptide production are conducted with regard to changes in cell volume. At molecular level, processes concerning mechanisms of gene expression induced by thyroid hormones or derivatives of retinoic acid, and focus is also on characteristics of nuclear receptors of biologically active substances in healthy and tumorous tissue.

 

The methodological approach includes methods of molecular biology and genetics in combination with physiological and biochemical techniques, and that both in the integrated organism and in isolated cells and tissues. The range of experimental animals used embraces animals with inborn and induced model derangements of serious diseases (diabetes, obesity, hyperlipidemia, hypertension, depression and cancer).

 

In the year 2000, in a strong international competition, bodies of the European Commission selected the Institute for nomination as Centre of Excellence. Out of 185 submitted projects, the Institute ranked fifth to eighth, and became the Centre of Excellence of the European Union. Experts of the European Commission acknowledged the orientation of the project, the significance of the topic, the multidisciplinary approach, the international cooperation involved and the expected positive impact of the results upon the European population. They underlined the characteristics of the Institute as a dynamically developing research facility with broadly established international cooperation, which can stand the proof with institutions in EU countries.

 

The positive assessment of the Institute was supported also by the high profile of its research workers: 12 of them hold the highest scientific degree (D.Sc.), the majority are internationally recognized scientists, regularly lecturing abroad, participating in international congresses, often as chairpersons of sections and invited lecturers.

 

In the research focus of the Laboratory of Molecular Endocrinology are investigations of the characteristics and functions of nuclear receptors of hormones, ligand-inducible transcription factors in the body. Fully operational nuclear receptors are indispensable not only for the biological activity of a great number of hormones but also for the efficacy of further biologically active substances. A variety of changes at the level of nuclear receptors may lead to suppression or even complete elimination of the response of the organism to the relevant hormone, which may in turn give rise to serious civilization diseases caused by partial or complete resistance of the body to the corresponding hormone. Study of the mechanism of action of thyroid hormones and of retinoic acid or vitamin D3 is aimed at elucidating the effect of endo- and exogenous factors on expression, affinity and concentration of transcription factors inducible by thyroid hormones and retinoic acid or vitamin D3 in the body, as well as at understanding the ability of these transcription factors to bind to specific DNA segments, so-called cis-acting responsive elements.

 

Also our research purpose is to contribute to the understanding of the characteristics and expression of nuclear receptors in normal, preneoplastic and in neoplastic tissue and to provide new information on potential modulation of nuclear receptor status in different experimental models in vitro and in vivo.

Contribution to CASCADE

Among the major interest of the Laboratory of Molecular Endocrinology, the first place takes the field of nuclear receptors. We have skills and data predominantly on retinoic acid receptors (RARs, RXRs), thyroid hormone receptors (TRs), dihydroxyvitamin D3 receptors (VDR) and their coregulators.

 

In general, we are capable to study the effects of a variety of toxic chemicals and/or food constitutents on a nuclear receptor expression, ligand-binding characteristics, nuclear receptor capability to bind to their cognate hormone responsive elements and perform routinely a number of experimental approaches and analyses that include:

 

- Both in vitro and in vivo animal experiments;

- Reverse transcription and subsequent quantitative Real-Time PCRs of nuclear receptors and their coregulators in animal tissues (liver, spleen, tumours, etc.) or human tissue (lymphocytes);

- EMSA or Supershift assays for binding of nuclear receptors to TRE, RARE or VDRE in both animal and human tissues;

- Scatchard plot analyses to determine Bmax and Ka of nuclear receptors for 3,5,3´-triiodothyronine or all-trans retinoic acid binding in rat liver, spleen or tumour tissue;

- Enzyme(s) activity analyses (type I iodothyronine 5´-deiodinase, tissue transglutaminase,    malic enzyme) in animal or human tissues;

- Animal model of mammary gland carcinogenesis for study of the effects of compounds and/or food constituents on development and progression of mammary gland tumours in virgin female Sprague-Dawley rats.

- Analyses on Micro-PET ”eXplore Vista SR” model, a dedicated positron emission tomograph for studies of rodents monitored by [F-18]-fluoro-2-deoxy-D-glucose or other short-life radiopharmaceutical preparations.  

Representative scientific articles as relevant to CASCADE:

Rock E., Winklhofer-Roob B.M., Ribalta J., Scotter M., Vasson M.P., Brtko J., Brigelius-Flohe R., Bronner A., Azais-Braesco V.: Vitamin A, vitamin E and carotenoid status and metabolism during ageing: Functional and nutritional consequences (VITAGE PROJECT). Nutr. Metab. Cardiovasc. Dis., 11: 70-73, 2001.

 

Brtko J., Bobáľová J., Podoba J., Schmutzler C., Köhrle J.: Thyroid hormone receptors and type I iodothyronine 5´-deiodinase activity of human toxic adenomas and benign cold nodules. Exp. Clin. Endocrinol. Diabetes, 110: 166-170, 2002.

 

Brtko J., Thalhamer J.: Renaissance of the biologically active vitamin A derivatives: Established and novel directed therapies for cancer and chemoprevention (Invited review). Curr. Pharm. Design, 9: 2067-2077, 2003.

 

Štefánik P., Macejová D., Mravec B., Brtko J., Križanová O.: Distinct modulation of a gene expression of the type 1 and 2 IP3 receptors by retinoic acid in brain areas. Neurochem. Int., 46: 559-564, 2005.

 

Macejová D., Rádiková Ž., Macho L., Liška J., Brtko J.: MNU-induced carcinogenesis of rat mammary gland: Effect of thyroid hormone on expression of retinoic acid receptors in tumours of mammary gland. Mol. Cell. Endocrinol., 244: 47-56, 2005.