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. 2004 Jul;91(3):157-70.
doi: 10.1016/j.jsbmb.2004.02.008.

Partitioning of 5alpha-dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol activated pathways for stimulating human prostate cancer LNCaP cell proliferation

Eva H Nunlist  1 , Igor Dozmorov, Yuhong Tang, Rick Cowan, Michael Centola, Hsueh-Kung Lin
Affiliations

Partitioning of 5alpha-dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol activated pathways for stimulating human prostate cancer LNCaP cell proliferation

Eva H Nunlist et al. J Steroid Biochem Mol Biol. 2004 Jul.

Abstract

The growth and development of the prostate gland are regulated by androgens. Despite our understanding of molecular actions of 5alpha-dihydrotestosterone (5alpha-DHT) in the prostate through the trans-activation of the androgen receptor (AR), comprehensive analysis of androgen responsive genes (ARGs) has just been started. Moreover, expression changes induced by the androgen effects of 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), a metabolite of 5alpha-DHT through the action of 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs), remain undefined. We demonstrated that both 5alpha-DHT and 3alpha-diol stimulated similar levels of androgen sensitive human prostate cancer LNCaP cell proliferation. However, consistent with the fact that 3alpha-diol has low affinity toward the AR, 3alpha-diol did not elicit the same levels of AR trans-activation activity as that of 5alpha-DHT. Since LNCaP cells respond to androgen stimulation by transcriptionally activating the AR downstream genes, gene expression patterns between 0 and 48 h following 3alpha-diol and 5alpha-DHT stimulation were analyzed using cDNA-based membrane arrays to define the temporal regulation of ARGs. Array analysis identified 217 and 219 androgen-modulated genes in at least one time point following 3alpha-diol and 5alpha-DHTstimulation, respectively, including key regulators of cell proliferation. Only a subset of these genes (143) was regulated by both androgens. These data suggest that 3alpha-diol exerts androgenic effects independent of the action of 5alpha-DHT in steroid target tissues. Accordingly, 3alpha-diol might activate cell proliferation cascades independent of AR pathway in the prostate.

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