Influence of diethylstilbestrol, Leuprolelin (a luteinizing hormone-releasing hormone analog), Finasteride (a 5 alpha-reductase inhibitor), and castration on the lobar subdivisions of the rat prostate.
The effects of various means of interfering with androgen action on rat coagulating gland, ventral prostate, lateral type 1 prostate, lateral type 2 prostate, and dorsal prostate were examined morphologically and quantitatively by assessing DNA content, wet weight, protein content, and zinc concentrations. Adult male Sprague-Dawley rats were subjected to 2 weeks of interfering with androgen action by treatment with Leuprolelin (a luteinizing hormone-releasing hormone analog), Finasteride (a 5 alpha-reductase inhibitor), or diethylstilbestrol (DES), or by physical castration. For all prostatic lobes, inhibition of 5 alpha-reductase elicited the smallest reduction in prostatic wet weight, DNA and protein contents, and zinc concentration. The most profound reductions in all parameters were elicited by castration. Treatments with DES and Leuprolelin gave intermediate effects with DES being the more effective in reducing all parameters in all prostatic lobes. Morphological changes elicited by all forms of androgen blockade were reduction of epithelial height, relative increase of connective tissue, reduction in ductal diameter, length, and number. The order of effectiveness of the various treatments on morphological features was as described above. While all forms of androgen blockade elicited similar effects throughout the prostate, differences in response to all forms of interference with androgen action were observed in different lobes of the prostate with regard to wet weight, DNA and protein contents, and zinc concentration as well as morphological effects. Regressive changes at the morphological level were particularly striking in the coagulating gland and ventral prostate, and indistinct in the lateral type 2 prostate. Prostatic zinc concentration in both normal and androgen-deprived rats was the highest in the lateral type 2 prostate and was reduced by interfering with androgen action to the greatest extent in the dorsolateral prostate (lateral type 1 and type 2, and dorsal prostate). The distribution of zinc correlated with the expression of metallothionein, which was detected by immunocytochemistry only in the lateral type 2 prostate of both normal and androgen deprived rats. Intraprostatic heterogeneity of zinc and metallothionein expression emphasizes interlobar differences in biological function within the rat prostate. The mechanism of development of regional heterogeneity within the prostate may shed light on the pathogenesis of prostatic proliferative diseases (prostatic hyperplasia and prostatic cancer) that initially owe their development to focal changes within large cell populations.
Yamashita
A
A
Department of Urology, Mie University, School of Medicine, Mieken, Japan.
Hayashi
N
N
Sugimura
Y
Y
Cunha
G R
GR
Kawamura
J
J
D058891:5-alpha Reductase Inhibitors; D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018120:Finasteride / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D008297:Male; D008969:Molecular Sequence Data; D009919:Orchiectomy; D009929:Organ Size; D011467:Prostate / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood; D015032:Zinc / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D011506:Proteins; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D018120:Finasteride; D004054:Diethylstilbestrol; D004247:DNA; D015032:Zinc