Reproduction and development


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Title Reproduction and development
Period 01 / 1988 - unknown
Status Completed
Research number OND1281086
Data Supplier METIS Erasmus Universiteit Rotterdam


Androgenic hormones play an essential role in the control of male sexual differentiation and development, and in the maintenance of normal male reproductive function. Androgens belong to the group of steroid hormones, and their action is mediated by a low-abundance nuclear receptor protein. Steroid hormone receptors form a family of ligand-responsive transcription regulators that also includes the retinoic acid receptor and the thyroid hormone receptor. In general, the response of a steroid hormone target cell depends on several intracellular processes, e.g. binding of the steroid hormone to its receptor, transformation of the receptor molecule to a DNA-binding form, interaction of the hormone-receptor complex with specific DNA-sequences (hormone responsive elements), and modulation of the transcription of specific genes. Although several aspects in the molecular mechanism of steroid hormone action appear common for all steroid hormones, differences have been observed with respect to subcellular receptor localization in the absence of hormone, the cellular regulation of the steroid binding activity of the receptor molecule, the specific interaction with hormone responsive elements of the hormone receptor complex, the type of hormone responsive elements, and the nature of other interacting proteins in the transcription initiation unit. Detailed knowledge of most of the different steps in androgen action, however, is not available. Disturbance of the androgen response at the transcriptional or translational level, or even at post-translational steps, might result in partial or complete androgen insensitivity, or in malignant transformation. Such pathological situations include pseudohermaphroditism and prostate carcinoma. In order to obtain more insight in the cellular regulation of the androgenic response in normal and pathological situations, it is essential to obtain detailed knowledge of the androgen receptor and androgen action. This action includes auto- or paracrine regulation by secreted factors. The program focusses on the following aspects: 1. Androgen receptor structure and function 2. Role of androgens and the androgen receptor during growth and differentiation 3. Analysis of the androgen receptor gene in the androgen insensitivity syndrome 4. Molecular aspects of development of androgen independent prostate cancer

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Project leader W.M. Baarends
Project leader L.J. Blok
Project leader Dr. A.O. Brinkmann
Project leader Prof.dr. J.A. Grootegoed
Project leader Prof.dr. A.K. Slob
Project leader Dr. J.T.M. Vreeburg


D21400 Genetics
D21700 Physiology
D23120 Oncology
D23220 Internal medicine

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