Cortisol alters gene expression during involution of the rat ventral prostate.
The ability of high doses of cortisol to retard the involution process in the rat ventral prostate was related to alterations in the pattern of gene expression. Poly(A)+ RNA preparations from the prostates of noncastrated, castrated, and castrated rats injected daily for 7 days with cortisol were compared by Northern blot hybridizations for the relative expression of genes associated with cell differentiation and maintenance (the C1 prostatic steroid binding protein gene and alpha-tubulin), with cell death (TRPM-2, hsp 70, and c-fos), and with hormone regulation (the androgen and glucocorticoid receptors). As anticipated, the concentration of C1 mRNA in the prostate fell to less than 4% of that in the noncastrated controls within 4 days after castration and was nearly undetectable after 7 days. This decline was retarded by cortisol treatment of 7-day castrated animals which sustained the level of C1 transcripts at approximately 50% of control. While the pattern of expression of alpha-tubulin indicated some minor fluctuations, with the highest level occurring 7 days after castration, the prostates of the cortisol-treated group had essentially the same concentration of this mRNA as the noncastrates. Cortisol also modified the expression of genes associated with prostatic cell death. The large increase in prostatic TRPM-2 mRNA, seen 7 days after castration, was reduced by over 80% after treatment with the glucocorticoid. Although not as abundantly expressed as TRPM-2, the castration-induced levels of transcripts for both hsp 70 and the protooncogene c-fos were substantially reduced by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)
Rennie
P S
PS
Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, Vancouver, Canada.
Bowden
J F
JF
Freeman
S N
SN
Bruchovsky
N
N
Cheng
H
H
Lubahn
D B
DB
Wilson
E M
EM
French
F S
FS
Main
L
L
D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D011987:Receptors, Steroid / Q000235:genetics
D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011987:Receptors, Steroid; D006854:Hydrocortisone