Estrogen Metabolism and Prostate Cancer Risk
Abstract
Prostate cancer is the most common non-skin cancer among men in industrialized countries (I). The causes of prostate cancer, however, remain largely unknown, with age, race, and family history being the only established risk factors (2). The prostate gland has historically been considered the prototype of an androgen-dependent organ. However, there is evidence that estrogens may induce mitosis of both normal and malignant prostatic epithelial cells in many species, including humans (3,4). In humans, 16alpha (16alpha-OHE1) and estriol are biologically significant estrogens, and their activity can contribute to the overall expression of estrogenic action. Hydroxylation of estrone at the 16alpha-position, one of the two major and mutually exclusive biotransformation pathways of the estrogens, leads to estrogen metabolites with estrogenic activity (5-7) and genotoxic characteristics (8). The other main pathway for estrogen metabolism is via hydroxylation at the C-2 position, producing 2-hydroxyestrone (2-OHEl), a derivative that has virtually no estrogenic activity (6, 7, 9,10). In addition to the estrogenic effects of the 16alpha-hydroxylated metabolites, in in-vivo models, 16alpha- hydroxylation of estrone was associated with increased spontaneous incidence of tumors (11).
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2001
- Accession Number
- ADA405357
Entities
People
- Paola C. Muti
Organizations
- University at Buffalo