INHIBITORY ACTIVITY OF ANALOGUES OF LUTEINIZING HORMONE‐RELEASING HORMONE (LH‐RH) IN VITRO AND IN VIVO

L. FERLAND, F. LABRIE, M. SAVARY, M. BEAULIEU, D. H. COY, E. J. COY, A. V. SCHALLY

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Improved inhibitors of LH-RH are those which, beside removal of the histidine residue at position 2 of LH-RH, include replacement of glycine at position 6 by a D-amino acid. A still better modification is replacement of the histidine residue at position 2 by D-phenylalanine. As examples, when tested in pituitary cells in culture, [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH, [Des-His2, D-Phe6]-LH-RH, [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH inhibit 50% of LH release induced by LH-RH at molar ratios (MR50S) of 3000, 500, 60, 1000, 150 and 25, respectively. [D-Phe2, D-Phe6, D-Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH have MR50 values of respectively 400, 100, and 75. When evaluated in vivo, some of the mentioned structural modifications permit inhibition of LH-RH action at molar ratios lower than observed in vitro. At a 500 molar ratio, [D-Phe2, Phe5, D-Phe6]-LH-RH inhibits the plasma LH rise induced by LH-RH by 75% up to 5 h after its injection. When administered at 12.00 hours at the dose of 2 mg, this analogue inhibits the spontaneous pro-oestrus LH surge and ovulation by 85 and 75%, respectively.

Original languageEnglish (US)
Pages (from-to)s279-s289
JournalClinical Endocrinology
Volume5
DOIs
StatePublished - Feb 1976
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'INHIBITORY ACTIVITY OF ANALOGUES OF LUTEINIZING HORMONE‐RELEASING HORMONE (LH‐RH) IN VITRO AND IN VIVO'. Together they form a unique fingerprint.

Cite this