From contraception to cancer: a review of the therapeutic applications of LHRH analogues as antitumor agents.

摘要

LHRH and its analogues produce profound antireproductive effects in both sexes of a variety of animal species. Although the LHRH agonists induce gonadotropin release, gonadal steroid secretion, ovulation, and spermatogenesis as an expression of their traditional profertility pharmacologic profile, they paradoxically and characteristically cause predominant antifertility effects which have been extensively evaluated for potential contraceptive purposes. These agonists produce their antireproductive effects in both males and females by common mechanisms, ultimately resulting in disruption of pituitary-gonadal function, depression of steroidogenesis, and inhibition of target organs dependent on such gonadal support. Similar antireproductive effects have been observed with the LHRH antagonists which competitively inhibit LHRH-induced gonadotropin secretion resulting in reduced blood gonadal steroid levels. Use of the inhibitory properties has been extended to cancer therapy based on the ability of the LHRH analogues (particularly the agonists) to inhibit the growth of steroid-dependent (responsive) tumors (e.g., mammary, prostate) similar to that produced by gonadectomy and antisteroid treatments. The use of these peptides for selected hormone-sensitive tumors presents a novel pharmacotherapeutic application for this class of drug.