Comparative activity of pulsed or continuous estradiol exposure on gene expression and proliferation of normal and tumoral human breast cells.

Intranasal administration of hormone replacement therapy presents an original plasma kinetic profile with transient estrogen levels giving rise to the concept of pulsed therapy. To further understand the molecular effects of this new therapy, we have compared the effects of pulsed and continuous estradiol treatments on two critical aspects of estradiol action: gene expression and cell proliferation. Cells were stimulated with estradiol as 1-h pulsed or 24-h continuous treatments at concentrations such that the 24-h exposure (concentration x time) was identical in both conditions.

Hormonal regulation of the androgen receptor expression in human prostatic cells in culture.

The regulation of the androgen receptor (AR) expression was studied using immunocytochemical and Western blot techniques on separate cultures of epithelial cells (PNT2) and fibroblasts of human prostate. In both cell types, immunocytochemistry revealed both nuclear and cytoplasmic staining. Treatment with DHT (5 x 10(-9) M) increased both the intensity of nuclear staining and the number of cells stained.

Pharmacological and molecular evidence for the expression of the two steroid 5 alpha-reductase isozymes in normal and hyperplastic human prostatic cells in culture.

Background: Whereas the embryological development of the human prostate is clearly dependent on steroid 5 alpha-reductase (5 alpha-R) type 2 expression, the respective expression of the two known isoforms (types 1 and 2) of 5 alpha-R in the adult human prostate remains unclear.

Methods: 5 alpha-R isoform mRNA expression (Northern blots and reverse transcriptase-polymerase chain reaction [RT-PCR]) and enzyme activity were studied in immortalized epithelial cells (NE) and in fibroblasts from normal (NF) or hyperplastic (BPHF) human prostates.

Results: 5 alpha-R activity (fmol/microgram DNA/hr) was 1.

Human prostatic cells in culture: different testosterone metabolic profile in epithelial cells and fibroblasts from normal or hyperplastic prostates.

The prostate gland depends on androgens for its development and the maintainance of its differentiated structures and secretory function. We have characterized the metabolic pathways of testosterone in isolated epithelial (NE) and fibroblast cultured cells from normal (NF) and hyperplastic (BPHF) prostates, in order to provide a tool for the study of androgen function in the prostate in defined conditions. In NE, 5 alpha-reductase (5 alpha-R) is the predominant metabolic pathway whereas in NF 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSDHase) is the main activity.

Predominant expression of 5 alpha-reductase type 1 in pubic skin from normal subjects and hirsute patients.

Dihydrotestosterone (DHT), the 5 alpha-reduced metabolite of testosterone, is the active molecule triggering androgen action, and 5 alpha-reductase (5 alpha-R), the enzyme converting testosterone to DHT, is a key step in this mechanism. Skin, like prostate, is a DHT- dependent tissue. Our laboratory demonstrated, many years ago, that 5 alpha-R in external genitalia was not regulated by androgens, whereas it was androgen dependent in public skin.