Polyamines in prostatic epithelial cells and adenocarcinoma; the effects of androgen blockade.
BACKGROUND
Recent identification of eosinophilic prostatic secretory granules (PSG) as the major secretory mechanism of the prostate gland and their loss in neoplasia has prompted scrutiny of their chemical constituents. Polyamines, in particular spermine and spermidine (sp/spd) are the major cations found within prostatic secretions, yet their secretory mechanism in normal and neoplastic tissues has not been investigated.


METHODS
Normal prostatic tissues and adenocarcinoma from intact and chemically castrated men were preserved in a glutaraldehyde-based fixative (Solufix((R))). Immunostains for sp/spd were performed before and after harsh acid hydrolysis whereby all protein was removed from tissue sections.


RESULTS
Sp/spd immunoreactivity correlated with PSG as recognized in routine stains in tissues from intact patients before and after acid digestion. Decrease in sp/spd in untreated carcinomas was directly related to loss of PSG. After chemical castration, normal glands were mostly devoid of sp/spd while surviving malignant cells stained positively, despite a significant reduction or absence of PSG. Similarly, cancers progressing after castration were intensely decorated with anti-spermine, despite an almost complete loss of PSG. Cytoplasmic sp/spd staining of these androgen resistant clones was in contrast to normal glands no longer acid resistant.


CONCLUSIONS
The intense eosinophilia of PSG is attributable to polyamines. Androgen blockade arrests sp/spd production in normal tissue. In contrast, sp/spd production continues in androgen resistant tumor clones, thereby uncoupling polyamines from their normal androgen dependent environment.
Cohen
R J
RJ
Uropath Pty Ltd., 41 Hampden Road, Nedlands, Western Australia, Australia. ronnie@urc.uwa.edu.au
Fujiwara
K
K
Holland
J W
JW
McNeal
J E
JE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000726:Androgen Antagonists / Q000494:pharmacology*; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D022142:Secretory Vesicles / Q000378:metabolism / Q000473:pathology; D013095:Spermidine / Q000032:analysis / Q000096:biosynthesis*; D013096:Spermine / Q000032:analysis / Q000096:biosynthesis*
D000726:Androgen Antagonists; D013096:Spermine; D013095:Spermidine