Signalling in reproduction and aging


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Title Signalling in reproduction and aging
Period 01 / 2006 - unknown
Status Completed
Research number OND1318998
Data Supplier Website MolMed


The overall goal of the research of the theme Signaling and ageing is to lay a biological foundation for treatment modalities in the clinic. Emphasis is on hormone signaling through receptors on the one hand and the physiological processes that occur with aging on the other. With respect to the signaling part of the theme we focus on transmembrane signaling by members of the TGFâ family of growth and differentiation factors and receptors that belong to the large family of G protein coupled receptors GPCRs, a family of high interest for drug development. These ligands and their receptors are studied in various physiological systems. One of those systems is the ovary, an organ that changes continuously throughout life, from follicle development, via the onset of puberty to the loss of menstrual cycling after menopause. We focus on the relationship between the dysfunction of the ovary in patients with polycystic ovary syndrome (PCOS) and the dysregulation of their metabolism, often displayed as obesity. We hypothesize that factors of the TGFâ family, such as AMH and BMPs, act on peripheral tissues such as fat tissue and play a role in the development of obesity in these women. A second major object of our studies is fat tissue, both white and brown fat tissue. Here we study the physiology of obesity and we try to develop new candidates for anti-diabetic drugs or drug targets. The focus here is on ghrelin and its unacylated form, UAG. Ghrelin and most probably UAG act through GPCRs and their target tissues include â-cells of the pancreas, fat and liver, all important players in the regulation of glucose and fat metabolism. A third area of our interest lies in the target organ sensitivity for steroid hormones. Many steroid hormones are further metabolized and activated by their target tissues, and this may have impact on treatment strategies for e.g. prostate and breast cancer. Lastly, we are striving to understand the molecular details of GPCR activation using the LH receptor, a receptor involved in the regulation of steroid hormone production in the gonads, as a model.

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Project leader Prof.dr. A.P.N. Themmen
Project leader Dr. R.F.A. Weber


D21700 Physiology
D23220 Internal medicine

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