当前位置： SCI文献检索 > EXPERT OPINION ON INVESTIGATIONAL DRUGS期刊下所有文献 > LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action.

LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action.

Abstract：

:Two classes of luteinising hormone-releasing hormone (LHRH) analogues have been developed so far to be used for oncological therapies: LHRH agonists and antagonists. LHRH agonists are widely and successfully used for the management of steroid-dependent malignancies. Chronic administrations of these compounds result in downregulation and desensitisation of pituitary LHRH receptors and, therefore, in a complete suppression of gonadal function. LHRH agonist administration is effective, safe and reversible, suffering only from the 'flare-up' phenomenon at the beginning of treatment. LHRH antagonists suppress the pituitary-gonadal function by competing with native LHRH for binding to its pituitary receptor but without giving rise to the intracellular cascade of events evoked by the natural hormone or LHRH agonists. Synthetic peptides belonging to the last generations of LHRH antagonists have already been successful in clinical trials. They are completely devoid of the 'flare-up' phenomenon and seem to be free of side effects, such as histamine release. Recently, the expression of LHRH and LHRH receptors has been reported in a number of hormone-responsive tumours. In contrast with the pituitary LHRH receptor which is coupled to the Gq/11-PLC intracellular system of events, stimulation of the tumour LHRH receptor by LHRH is followed by the activation of a Gi protein and a decrease in cAMP levels. This intracellular pathway mediates the inhibitory action of the autocrine/paracrine LHRH system on tumour cell proliferation. The activation of LHRH receptors at tumour level may then represent an additional and more direct mechanism of action for the antitumoural activity of LHRH agonists. Surprisingly, LHRH antagonists also exert a marked antimitogenic activity on a number of hormone-responsive cancer cell lines, indicating that these compounds might behave as antagonists at pituitary level and as agonists at the level of the tumour. The observation that the inhibitory LHRH autocrine system is also present in some steroid-unresponsive cancer cell lines might suggest a possible clinical utility of LHRH analogues also for those tumours that have escaped the initial phase of hormone dependency.

journal_name

Expert Opin Investig Drugs

journal_title

Expert opinion on investigational drugs

authors

Limonta P,Montagnani Marelli M,Moretti RM

doi

10.1517/13543784.10.4.709

subject

Has Abstract

pub_date

2001-04-01 00:00:00

pages

709-20

issue

eissn

1354-3784

issn

1744-7658

journal_volume

pub_type

杂志文章,评审

在线工具

LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action.