Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2005) 9 S19

BES2005 Symposia Symposium 4: Intracellular transport for steroids (4 abstracts)

Intracellular trafficking of vitamin D receptors and interacting proteins

J Barsony 1 & 2


1Division of Endocrinology, Georgetown University, Washington, DC, USA; 2Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.


The hormonal form of vitamin D, calcitriol, regulates diverse cellular functions through activation of the vitamin D receptor (VDR), in a manner similar to how other ligands of nuclear receptors elicit regulation of gene transcription. Insufficient or excess calcitriol responses manifest primarily as bone diseases (rickets, osteoporosis, Paget's diseases) and hyperproliferative diseases (psoriasis and cancer). Our long-term objective is to elucidate the molecular mechanisms that regulate VDR functions and therefore provide insight into the origin of these diseases. We used advanced microscope imaging techniques (FRAP, FLIP, FRET, iFRET, 4D motion analysis) combined with genetic and biochemical approaches to explore the spatial and temporal regulation of calcitriol actions. We synthesized fluorescing derivatives to visualize hormone uptake and the subcellular trafficking of the liganded VDR. Our studies indicated that transcriptional regulation by VDR is a highly dynamic and sequential process. The rules that determine the subcellular location of calcitriol, VDR, and the interacting proteins (retinoid X receptor, corepressors, coactivators, chaperones, transport proteins, proteases) determined the stoichiometry and probability of their interactions, and thus determined the magnitude, duration, and selectivity of VDR transcriptional activities in cultured kidney-derived cells. We also synthesized novel VDR antagonists that allowed us to selectively control VDR interactions with coregulators, and thereby control breast cancer growth in cultured cells and in mice without causing toxic side effects, such as hypercalcemia. Taken together these studies revealed fundamental pathways of calcitriol actions and provided the basis for the development of strategies to selectively alter VDR targeting.

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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