Luteinising hormone-releasing and anti-fertility properties of a glucagon-selective somatostatin analogue.
The hypothalamic tetradecapeptide, somatostatin (SRIF), inhibits the secretion of growth hormone (GH) and numerous other hormones, including insulin and glucagon. Attempts to use SRIF as an adjunct in the treatment of diabetes mellitus met with limited success due to its short biological half-life and the undesirable diabetogenic activity of its insulin-lowering properties. Efforts at synthesis have yielded SRIF derivatives with prolonged GH-lowering activity which did not suppress glucagon or had equivalent insulin-inhibiting activity as well as several short-acting compounds with the appropriate glucagon specificity. A dodecapeptide analogue [des-Ala, Gly] His-D-Trp-SRIF (Wy-41, 747) has been identified that combines selective inhibition of GH and glucagon release with prolonged activity. However, in routine pharmacological tests chronic treatment of mature rats with Wy-41, 747 produced anti-reproductive effects resembling those described for luteinising hormone (LH)-releasing hormone (RH) and its agonists. We report here that Wy-41, 747, unlike SRIF and other of its analogues tested, releases LH, induces ovulation and inhibits pregnancy when administered before or after implantation; these properties are traditionally associated with the separate LH-releasing class of peptides.[1]References
- Luteinising hormone-releasing and anti-fertility properties of a glucagon-selective somatostatin analogue. Bex, F.J., Corbin, A., Sarantakis, D., Lien, E. Nature (1980) [Pubmed]
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