Antagonistic analogs of growth hormone-releasing hormone

New potential antitumor agents

Andrew V Schally, Jozsef L. Varga

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Recently, new potent antagonistic analogs of growth hormone-releasing hormone (GH-RH) have been synthesized. These GH-RH antagonists bind to pituitary receptors for GH-RH and inhibit the release of GH in vitro and in vivo. This suggests that they could be clinically useful in conditions such as acromegaly. The main applications of GH-RH antagonists would be in the field of insulin-like growth factor I (IGF-I)- and IGF-II-dependent cancers. GH-RH antagonists inhibit the growth of various human cancer cell lines xenografted into nude mice, including mammary cancers, androgen-independent prostate cancers, small-cell lung carcinomas, non-small-cell lung carcinomas, renal adenocarcinomas, pancreatic cancers, colorectal carcinomas and malignant gliomas. These effects could, in part, be exerted indirectly through inhibition of the secretion of GH and the resulting reduction in levels of hepatic IGF-I. However, the principal action of GH-RH antagonists in vivo appears to be the direct suppression of the autocrine and/or paracrine production and expression of the genes encoding IGF-I (IGF1) and IGF-H (IGF2) in tumors. In vitro, antagonists of GH-RH inhibit the proliferation of mammary, prostatic, pancreatic and colorectal cancer cell lines, reducing the expression of IGF2 mRNA in the cells and the secretion of IGF-II. The presence of the GH-RH ligand has been demonstrated in human ovarian, endometrial, mammary and lung cancers, suggesting that GH-RH could be a growth factor. Further development of GH-RH antagonists should lead to potential therapeutic agents for IGF-dependent cancers.

Original languageEnglish
Pages (from-to)383-391
Number of pages9
JournalTrends in Endocrinology and Metabolism
Volume10
Issue number10
DOIs
StatePublished - Dec 1 1999
Externally publishedYes

Fingerprint

Growth Hormone-Releasing Hormone
Antineoplastic Agents
Hormone Antagonists
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Breast Neoplasms
Pancreatic Neoplasms
Colorectal Neoplasms
Neoplasms
Prostatic Neoplasms
Cell Line
Acromegaly
Small Cell Lung Carcinoma
Endometrial Neoplasms
Renal Cell Carcinoma
Nude Mice
Non-Small Cell Lung Carcinoma
Glioma
Ovarian Neoplasms
Androgens

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Antagonistic analogs of growth hormone-releasing hormone : New potential antitumor agents. / Schally, Andrew V; Varga, Jozsef L.

In: Trends in Endocrinology and Metabolism, Vol. 10, No. 10, 01.12.1999, p. 383-391.

Research output: Contribution to journalArticle

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