EFFECTS OF NEONATAL ESTROGEN EXPOSURE ON PROSTATIC SECRETORY GENES AND THEIR CORRELATION WITH ANDROGEN RECEPTOR EXPRESSION IN THE SEPARATE PROSTATE LOBES OF THE ADULT-RAT

Brief administration of estrogen to newborn rats permanently restricts prostatic growth and testosterone sensitivity in adulthood. Previous work demonstrated that neonatal exposure to estradiol benzoate produce d lobe-specific imprints in prostatic androgen receptor (AR) expressio n. Epithelial cell AR was markedly reduced or absent in the adult vent ral and dorsal lobes, which correlated with a lack of epithelial diffe rentiation and responsiveness. While the lateral lobe also showed redu ced growth and testosterone responsiveness after neonatal estradiol be nzoate, normal cell differentiation and AR levels were observed within the adult epithelium. To determine the impact that these receptor imp rints have on the functional capacity of adult tissue, we herein exami ned the expression of lobe-specific, androgen-dependent, or androgen-r esponsive secretory genes in prostates of rats given neonatal estradio l benzoate and directly compared this with epithelial cell AR using hi stological techniques. Sprague-Dawley rat pups were given 25 mug estra diol benzoate or oil on days 1, 3, and 5 and killed on day 90. Prostat ic mRNA was analyzed using Northern blots and in situ hybridization. V entral lobe mRNA was hybridized with a prostate binding protein (PBP) cDNA probe, while lateral and dorsal mRNA were hybridized with RWB (se minal vesicle secretory protein or SVS-II), probasin, and DP1 cDNA pro bes. Sections adjacent to those used for in situ hybridization were st ained for AR by immunocytochemistry. Neonatal estradiol benzoate signi ficantly reduced ventral lobe PBP message on Northern blots, and this was not restored with adult testosterone administration. There was a d irect correlation between epithelial cell AR and PBP expression, in th at PBP message and protein were only present in epithelial AR-positive cells and were absent in all AR-negative epithelium. In the lateral p rostate, probasin expression was unaffected by neonatal estradiol benz oate, whereas RWB was slightly reduced using Northern analysis. By in situ hybridization, these messages were observed at normal levels in l ateral lobe epithelial cells of estrogenized rats, which directly corr elated with the presence of AR in those cells. In the dorsal prostate, different response patterns to neonatal estradiol benzoate were found for the three secretory genes analyzed. On Northern blots, DP1 messag e significantly declined, probasin mRNA was modestly suppressed, and R WB expression was significantly elevated compared to those in control tissue. In situ hybridization revealed that RWB expression in estrogen ized dorsal lobes was amplified in AR-positive epithelial cells, where as AR-negative cells appeared unaltered. In summary, prostatic functio nal activity after neonatal estradiol benzoate exposure is affected in a lobe-specific manner, which correlates with the AR imprints in the separate lobes.