Effects of adrenal androgens on the transplantable human prostate tumor PC-82.
The potential of the adrenal androgens androstenedione (A) and dehydroepiandrosterone (DHEA) to stimulate prostate tumor growth was investigated in the hormone-dependent human prostate tumor model PC-82, propagated in nude mice. Substitution of castrated mice bearing growth-arrested tumors with DHEA for 28 days, resulting in peripheral levels of 9.2 +/- 1.7 nmol/liter (mean +/- SEM), led to a decline of tumor burden comparable to that observed in castrated controls. Intratumor testosterone (T) and 5 alpha-dihydrotestosterone were similar to those detected in the castrated group. In contrast, high-dose A supplementation (peripheral level of 13.5 +/- 1.3 nmol/liter) in androgen ablated tumor-bearing mice resulted in tumor growth, although less pronounced than in T-resubstituted mice (T level of 18.8 +/- 1.5 nmol/l). Intraprostatic levels of androgens were not different between both groups. Substitution of castrated PC-82 tumor-bearing mice with low-dose A (2.5 +/- 0.4 nmol/l) neither stimulated growth of tumors nor did it lead to regression of PC-82 tumors. Proliferative activity as estimated by BrdU incorporation (S-phase cells) was not induced in these tumors. In conclusion, DHEA does not have a stimulatory effect on growth of PC-82 tumor tissue, but A is capable of inducing PC-82 tumor growth, most likely through peripheral conversion of A into T and 5 alpha-dihydrotestosterone.
van Weerden
W M
WM
Department of Urology, Erasmus University, Rotterdam, The Netherlands.
van Kreuningen
A
A
Elissen
N M
NM
de Jong
F H
FH
van Steenbrugge
G J
GJ
Schröder
F H
FH
D000735:Androstenedione / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000473:pathology*; D013739:Testosterone / Q000097:blood; D014407:Tumor Cells, Cultured
D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D001973:Bromodeoxyuridine