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 produced lobe-specific imprints in prostatic androgen receptor (AR) expression. Epithelial cell AR was markedly reduced or absent in the adult ventral and dorsal lobes, which correlated with a lack of epithelial differentiation and responsiveness. While the lateral lobe also showed reduced growth and testosterone responsiveness after neonatal estradiol benzoate, normal cell differentiation and AR levels were observed within the adult epithelium. To determine the impact that these receptor imprints have on the functional capacity of adult tissue, we herein examined the expression of lobe-specific, androgen-dependent, or androgen-responsive secretory genes in prostates of rats given neonatal estradiol benzoate and directly compared this with epithelial cell AR using histological techniques. Sprague-Dawley rat pups were given 25 micrograms estradiol benzoate or oil on days 1, 3, and 5 and killed on day 90. Prostatic mRNA was analyzed using Northern blots and in situ hybridization. Ventral lobe mRNA was hybridized with a prostate binding protein (PBP) cDNA probe, while lateral and dorsal mRNA were hybridized with RWB (seminal vesicle secretory protein or SVS-II), probasin, and DP1 cDNA probes. Sections adjacent to those used for in situ hybridization were stained for AR by immunocytochemistry. Neonatal estradiol benzoate significantly reduced ventral lobe PBP message on Northern blots, and this was not restored with adult testosterone administration. There was a direct correlation between epithelial cell AR and PBP expression, in that PBP message and protein were only present in epithelial AR-positive cells and were absent in all AR-negative epithelium. In the lateral prostate, probasin expression was unaffected by neonatal estradiol benzoate, whereas RWB was slightly reduced using Northern analysis. By in situ hybridization, these messages were observed at normal levels in lateral lobe epithelial cells of estrogenized rats, which directly correlated 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 message significantly declined, probasin mRNA was modestly suppressed, and RWB expression was significantly elevated compared to those in control tissue. In situ hybridization revealed that RWB expression in estrogenized dorsal lobes was amplified in AR-positive epithelial cells, whereas AR-negative cells appeared unaltered. In summary, prostatic functional activity after neonatal estradiol benzoate exposure is affected in a lobe-specific manner, which correlates with the AR imprints in the separate lobes.
Prins
G S
GS
Department of Obstetrics and Gynecology, Michael Reese Hospital, University of Illinois College of Medicine, Chicago 60616.
Woodham
C
C
Lepinske
M
M
Birch
L
L
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics; D015152:Blotting, Northern; D004967:Estrogens / Q000008:administration & dosage* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009929:Organ Size; D011467:Prostate / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*
D004967:Estrogens; D012333:RNA, Messenger; D011944:Receptors, Androgen