EFFECTS OF CERTAIN ANALOGUES OF SYNTHETIC LUTEINIZING HORMONE RELEASING HORMONE ON THE RELEASE OF LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE IN THE ANOESTROUS EWE

Abstract

The ability of eight nonapeptide analogues of synthetic luteinizing hormone releasing hormone (LH-RH) to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the anoestrous ewe was studied and compared with the activity of synthetic LH-RH. In all the analogues, the glycineamide residue in position 10 was replaced with ethylamine; seven of them also had various substituents in positions 6 and/or 7. In a screening experiment using a single i.v. dose, the majority of the analogues were more potent than synthetic LH-RH in terms of the total amounts of LH and FSH released. The most potent overall was [d-Ser(But)6] Des Gly-NH210 LH-RH ethylamide which produced LH and FSH responses in terms of peak height, duration and area within the physiological range of the natural preovulatory peak. The dose–response relationships of this analogue and synthetic LH-RH were also compared. Deviations from parallelism were observed when all the aspects of the LH and FSH responses were considered, and with the FSH response deviations from linearity were also seen. These facts precluded the computation of a potency estimate using conventional statistical methods for the analysis of six-point biological assays, although it was clear that the analogue was substantially more potent than synthetic LH-RH. It was calculated that the administration of a single i.v. dose of between 6 and 30 μg of the analogue to anoestrous ewes would result in peaks in the concentrations of LH and FSH similar in all respects to those occurring naturally at oestrus, a situation previously found impossible to mimic with single injections of synthetic LH-RH.