Human Adrenal Androgens: Regulation of Biosynthesis and Role in Estrogen-Responsive Breast Cancer in a Mouse Model
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1996
- Accession Number
- ADB219065
Entities
People
- Peter J. Hornsby
Organizations
- Baylor College of Medicine