The effect of estrogen supplementation on cell proliferation and expression of c-kit positive cells in the rat prostate.
BACKGROUND
Benign prostatic hyperplasia (BPH) is associated with the proliferation of prostate tissue and an increase in smooth muscle tone. However, the way in which the hormonal environment affects cell proliferation and prostatic interstitial cells (PIC) responsible for the maintenance of the smooth muscle tone is not clear. The present study investigated the effect of estrogen supplementation on cell proliferation, androgen/estrogen ratio, and expression and/or distribution of PIC.


METHODS
Male Sprague-Dawley rats were anesthetized with isoflurane/oxygen breathing mixture and subcutaneously implanted with silastic capsules. These capsules were either empty or filled with a 10 or 20 mg of crystalline estrogen.


RESULTS
Estrogen exerted a potent effect on ventral prostate weight, which was manifested as a significant decrease between controls and the E(10)- and E(20)-treated rats. Active cell proliferation detected as Ki67-positive nuclei was observed in the stromal and epithelial cells of the ventral prostatic lobes from estrogen-treated rats and controls. Estrogen supplementation caused a significant and dose-dependent increase in prostatic estradiol and 5alpha-dihydrotestosterone (DHT) concentration but the ratios of either DHT/E(2) or E(2)/DHT were not significantly affected. PIC were observed in the region between the fibromuscular stroma and the glandular epithelium in all three experimental groups. E(20)-treated rats showed a higher expression of PIC than controls and E(10)-treated rats.


CONCLUSIONS
The present study provides novel information regarding the synergistic role of estrogens and androgens in the prostate: estrogen may prevent prostatic hyperplasia via mechanisms other than affecting cell proliferation or DHT/estrogen ratio.
Kusljic
Snezana
S
Department of Nursing, University of Melbourne, Carlton, Victoria, Australia.
Exintaris
Betty
B
D000728:Androgens / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019587:Dietary Supplements; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011470:Prostatic Hyperplasia / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D004967:Estrogens; D019394:Ki-67 Antigen; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D019009:Proto-Oncogene Proteins c-kit