Letter | Published:

Luteinising hormone-releasing and anti-fertility properties of a glucagon-selective somatostatin analogue

Abstract

The hypothalamic tetradecapeptide, somatostatin (SRIF), inhibits the secretion of growth hormone (GH)1 and numerous other hormones2, including insulin and glucagon3,4. Attempts to use SRIF as an adjunct in the treatment of diabetes mellitus5,6 met with limited success due to its short biological half-life7,8 and the undesirable diabetogenic activity of its insulin-lowering properties3,9,10. Efforts at synthesis have yielded SRIF derivatives with prolonged GH-lowering activity which did not suppress glucagon or had equivalent insulin-inhibiting activity11–14 as well as several short-acting compounds with the appropriate glucagon specificity15,16. A dodecapeptide analogue [des-Ala1, Gly2] His4,5-D-Trp8-SRIF (Wy-41, 747) has been identified that combines selective inhibition of GH and glucagon release with prolonged activity17,18. 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 agonists19–25. 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.

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