|
Gamma Linolenic Acid and Alpha Linolenic Acid Androgen action: molecular
mechanism and medical application.
Author: Liao S
Journal: Journal of Formos
Medical Association: 1994 Sep; 93 (9): 741-51
Abstract: Androgen action in many
organs, such as prostate and skin, is dependent on the conversion of
testosterone by 5 alpha-reductase to 5 alpha-dihydrotestosterone. 5
alpha-Dihydrotestosterone then binds to the androgen receptor to regulate
specific gene expression. Inhibitors of 5 alpha-reductase are useful for the
selective treatment of prostatic cancer, benign prostate hyperplasia, acne,
baldness and female hirsuitism, without affecting spermatogenesis, sexual
behavior and smooth muscle growth, that do not require the conversion of
testosterone to 5 alpha-dihydrotestosterone. Certain unsaturated fatty acids,
such as gamma-linolenic acid, are potent 5 alpha-reductase inhibitors,
suggesting a linkage between unsaturated fatty acids and androgen action.
Mutations in androgen receptor genes are responsible for many cases of
androgen-insensitivity. In some prostate cancer cells, some antiandrogens may
act like androgens in stimulating the proliferation of the cancer cells because
these antiandrogens can bind to a mutated androgen receptor and transactivate
target genes. Prostate cancers are usually androgen-dependent initially but can
lose dependency and responsiveness. Tumor cells which are resistant to endocrine
therapy ultimately proliferate. Androgen-independent or androgen-repressive
cells can arise from androgen-sensitive prostate cancer cells by changes in
specific gene expression over time in a clonal isolate. This change in androgen
responsiveness was accompanied by a change in androgen receptor expression and
transcriptional activity as well as expression of some oncogenes.
|
