Human Adrenal Androgens: Regulation of Biosynthesis and Role in Estrogen-Responsive Breast Cancer in a Mouse Model
Annual rept. 1 Sep 95-31 Aug 96
BAYLOR COLL OF MEDICINE HOUSTON TX
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These experiments investigate a mouse model of human adrenal androgen biosynthesis and the role of these steroids in human breast cancer growth. The main aim is to provide zone reticularis function in the human organoids in the mouse, because this zone synthesizes adrenal androgens dehydroepiandrosterone, DHEA. Pure zone reticularis cells implanted as organoids secreted cortisol but little DHEA. Two approaches are currently being tested first, to form an organoid with a capillary bed adequate for proper zonation to be re-established, and second, the genetic engineering of clonal adrenal cells to suppress 3beta-hydroxysteroid dehydrogenase 3beta-HSD, the key enzyme regulating DHEA biosynthesis. Additionally, investigation of the regulatory region of the 3beta-HSD gene has shown zonal differences in protein binding. The characterization of these transcription factors may provide future information on the molecular basis of zonation and thus indicate methods for obtaining zone reticularis function in the organoids.
- Anatomy and Physiology