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Endocrinology is the science of the endocrine glands, hormones and endocrine diseases. Classical hormones, paracrine signals and nutritional metabolites regulate all aspects of life including metabolism, development and ageing. The timely and sufficient supply of macro- and micronutrients including vitamins and trace elements is pivotal for the endocrine system, for regular growth, dynamic homeostasis and disease prevention. Recently, the trace element selenium (Se) has been identified as an essential component of our diet affecting risk and course of major endocrine and autoimmune diseases and cancer at various sites. Our research aims to better characterize the molecular basis of these interactions with a special focus on autoimmune thyroid diseases, diabetes mellitus, sepsis and tumorigenesis.
Thyronamines- Novel Endocrine Messengers
In addition, specific thyroid hormone derivatives, the so-called thyronamines, have been described as novel endocrine messengers. We aim to better characterize their molecular mode of action. To this end, we aim to choose a translational approach covering the development of novel diagnostic assays, cell culture work and experiments in model systems and finally including epidemiological analyses in collaboration with our clinical colleagues.
In the course of our recent work, we were focusing on the interaction of the selenium status with thyroid gland functioning and autoimmune thyroid diseases (10). We were able to identify novel functions of the selenium-transporter selenoprotein P as being of central importance for bones (4) and sperm quality (5). Moreover, we showed for the first time a direct association of selenium status with bone turnover in humans (8), and verified the association of colon cancer risk with selenium and selenoprotein P concentrations (2). We succeeded in identifying copper as a novel thyroid hormone-responsive blood biomarker (9), and in developing a novel assay for a potential biomarker of endocrine orbitopathy (6). We contributed to the generation and characterization of a novel mouse model for a rare selenoprotein-dependent inherited disease (1), identified the oxygen status as being of prime importance for regular selenoprotein expression (3), and characterized some newly synthesized selenocompounds as pharmacological lead structures potentially suitable as novel highly effective chemotherapeutics with little side-effects (7).
Novel Diagnostic Methods
At present, our repertoire of endocrine-specific diagnostic assays is enlarged, used to analyze comprehensive epidemiological studies in order to better understand the interaction of endocrine and cancer disease risk with the selenium and autoimmune status thereby improving disease prevention and patient care. Our research has identified important sex-specific differences which need to be taken into account when endocrine and autoimmune diseases and micronutrient interactions are studied and discussed.
10 Selected Publications
1. Seeher S, et al. Secisbp2 is essential for embryonic development and enhances selenoprotein expression. Antioxid Redox Signal. 2014 Aug 20;21(6):835-49.
2. Hughes DJ, et al. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort. Int J Cancer. 2014 Jul 9.
3. Becker NP, et al. Hypoxia reduces and redirects selenoprotein biosynthesis. Metallomics. 2014 May;6(5):1079-86.
4. Pietschmann N, et al. Selenoprotein P is the essential selenium transporter for bones. Metallomics. 2014 May;6(5):1043-9.
5. Michaelis M et al. Selenoprotein P in seminal fluid is a novel biomarker of sperm quality. Biochem Biophys Res Commun. 2014 Jan 17;443(3):905-10.
6. Minich WB, et al. Autoantibodies to the IGF1 receptor in Graves' orbitopathy. J Clin Endocrinol Metab. 2013 Feb;98(2):752-60.
7. Ibáñez E, et al. Structure- and cell-specific effects of imidoselenocarbamates on selenoprotein expression and activity in liver cells in culture. Metallomics. 2012 Dec;4(12):1297-307.
8. Hoeg A, et al. Bone turnover and bone mineral density are independently related to selenium status in healthy euthyroid postmenopausal women. J Clin Endocrinol Metab. 2012 Nov;97(11):4061-70.
9. Mittag J, et al. Serum copper as a novel biomarker for resistance to thyroid hormone. Biochem J. 2012 Apr 1;443(1):103-9.
10. Schomburg L. Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol. 2011 Oct 18;8(3):160-71.