Suramin inhibits gonadotropin action in rat testis: implications for treatment of advanced prostate cancer.
Suramin is being evaluated for the treatment of metastatic prostate cancer based on its inhibition of growth factor action. In addition, suramin may inhibit the endocrine control of androgen production, which was explored herein. Adult Sprague-Dawley rats were injected (i.p.) daily with varying doses of suramin. At a cumulative dose of 200 mg., suramin significantly depressed serum testosterone (p less than 0.05), and follicle stimulating hormone (p less than 0.002) levels. In vitro studies showed that suramin-mediated suppression of androgen production might be secondary to inhibition of gonadotropin action. In MA-10 cell cultures, suramin inhibited a maximum stimulatory dose of human chorionic gonadotropin with an ED50 of 4.4 microM. Studies in rat Sertoli cell cultures showed that follicle stimulating hormone action was also inhibited by suramin, with an ED50 of 8.6 microM. Using receptor binding assays with calf testis membrane, we showed that suramin inhibited 125I-hFSH binding to receptor in a dose dependent fashion with an ED50 of 10.4 microM; comparable to the ED50 of suramin inhibition of follicle stimulating hormone action in Sertoli cell culture cells. Thus the mechanism of suramin's suppression of androgen production may involve multiple sites of action, including inhibition of gonadotropin binding to its receptor and suppression of pituitary gonadotropin levels in serum. This inhibition of androgen production may be useful in the treatment of advanced prostate cancer.
Daugherty
R L
RL
Department of Urology, University of Rochester, New York.
Cockett
A T
AT
Schoen
S R
SR
Sluss
P M
PM
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors*; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors*; D008297:Male; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells; D013498:Suramin / Q000494:pharmacology*
D013498:Suramin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone