The prostate growth stimulation by progesterone is due to androgenic products and progesterone receptor-mediated mechanisms.
The antiprogestin mifepristone has been demonstrated to inhibit the growth of R3327HI rat prostatic carcinoma. A comparable antitumor effect of onapristone (ON) on rat Dunning tumors was found in our laboratories. We found the localization of progesterone (P4) receptors (PR) in prostate and prostatic tumors. These findings suggest the involvement of P4 in the mechanism of hormone-dependent growth of prostate and tumors. To study the influence of P4 on the growth of ventral (VP) and dorsolateral prostate (DLP), orchiectomized rats were treated (s.c.) daily with P4 (0.3, 1.0, 3.0 or 10.0 mg), dihydrotestosterone (DHT, 0.05 mg), estradiol (E2, 3.0 microg), ON (3.0 mg), ICI 182780 (1.0 mg) or flutamide (FL, 3.0 mg) for 12 days. One day after the last treatment, animals were sacrificed, and the organ weight of VP and DLP was determined. P4 increased the organ weight of VP and DLP in a dose-dependent manner. In contrast to DHT, which preferentially stimulated the growth of VP, P4 led rather to an increase in the weight of DLP. The effect of P4 on the DLP was enhanced by a simultaneous application of DHT or E2. The antiprogestin ON and the pure antiestrogen ICI 182780 had no appreciable effect on the P4-induced growth of VP and DLP. ON inhibited, however, the E2/P4-induced growth of DLP without affecting the growth of the VP. In contrast the antiandrogen FL suppressed the stimulatory effect of P4 on both the VP and DLP. These findings suggest that the stimulatory effect of P4 on the rat DLP may be partly due to androgenic products derived from P4 and may be also mediated by PR.
Nishino
T
T
Dr. Knoell Consult GmbH, Mannheim, Germany. tnishino@dr-knoell-consult.com
Ishibashi
K
K
Hirtreiter
C
C
Nishino
Y
Y
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D006067:Gonanes / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects / Q000254:growth & development*; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000187:drug effects*; D013268:Stimulation, Chemical
D000728:Androgens; D006067:Gonanes; D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol; C053238:onapristone