Changes in gene expression following androgen receptor blockade is not equivalent to androgen ablation by castration in the rat ventral prostate.
Involution of the rat ventral prostate and concomitant modulation of gene expression post-castration is a well- documented phenomenon. While the rat castration model has been extensively used to study androgen regulation of gene expression in the ventral prostate,it is not clear whether all the gene expression changes post-castration are due to androgen depletion alone. To obtain insights into this, we performed differential display reverse transcriptase polymerase chain reaction (DD-RT-PCR) which resulted in the identification of castration and/or flutamide-regulated genes in the rat ventral prostate. These include clusterin, methionine adenosyl transferase II alpha, and prostate-specific transcripts such as PBPC1BS, S100RVP and A7. While clusterin, PBPC1BS and methionine adenosyl transferase II alpha are regulated by both castration and flutamide, S100 RVP and A7 are regulated by castration alone. Interestingly, we show that flutamide, unlike castration, does not induce apoptosis in the rat ventral prostate epithelium, which could be an underlying cause for the differential effects of castration and flutamide treatment. We propose that castration leads to enrichment and depletion of stromal and epithelial cell types, respectively, resulting in erroneous conclusions on some of the cell type-specific transcripts as being androgen regulated.
Limaye
Anil M
AM
Chromatin Biology Lab, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India.
Asangani
Irfan
I
Kalyani
Thyagarajan
T
Kondaiah
Paturu
P
D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005485:Flutamide / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D017931:DNA Primers; D011944:Receptors, Androgen; D005485:Flutamide