Potentiating effect of buserelin acetate, an LHRH agonist, on the proliferation of ventral prostatic epithelial cells in testosterone-treated castrated rats.
BACKGROUND
We used buserelin acetate ([D-Ser(But)6] LHRH ), an LHRH agonist and strong blocker of LH secretion, as a treatment for prostatic cancer. It is possible that this LHRH agonist has a proliferative effect on the prostate in addition to suppressing LH secretion. The purpose of this study was to examine the proliferative effect of LHRH agonist on rat prostatic epithelial cells.


METHODS
We determined the optimal dose of testosterone necessary to maintain a positive level of proliferating cell nuclear antigen (PCNA) in the ventral prostatic epithelial cells of castrated Wistar rats. Testosterone-treated rats then received various doses of buserelin acetate. Castrated rats without exogenous testosterone also received buserelin acetate. The PCNA positivity was determined by immunohistochemistry with anti-PCNA monoclonal antibody.


RESULTS
The optimal dose of testosterone enanthate was 4 mg at 0 and 28 days after castration. Administration of buserelin acetate on day 0 and 28 in doses of 0.16 mg to 1.28 mg significantly increased PCNA positivity in a dose-dependent manner. Administration of buserelin acetate to castrated rats without testosterone also increased PCNA positivity but there was no statistical significance.


CONCLUSIONS
Buserelin acetate has a potentiating effect on the proliferation of ventral prostatic epithelial cells of castrated rat in the presence of a physiological level of exogenous testosterone. This effect may slightly influence the result of hormonal therapy by LHRH agonist.
Maezawa
H
H
Department of Urology, Yamanashi Medical University, Nakakoma-gun, Japan.
Komatsu
H
H
Kawaoi
A
A
Ueno
A
A
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002064:Buserelin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry; D003272:Contraceptive Agents, Male / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009919:Orchiectomy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D003272:Contraceptive Agents, Male; D018809:Proliferating Cell Nuclear Antigen; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D002064:Buserelin