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A tetradecapeptide with the proposed structure of growth hormone release inhibiting factor was synthesized by a classical fragment approach.

Addition of increasing doses of synthetic growth hormone-release inhibiting hormone (GH-RIH) leads to a progressive decrease of the basal and N 6 monobutyryl cyclic AMP-,theophylline- and prostaglandin E 2 -induced release of immunoreactive growth hormone (GH) and thyrotropin (TSH) release from rat anterior pituitary cells in monolayer culture. A halfmaximal effect is measured at 3 × 10 −9 M GH-RIH while a maximal inhibition to 10–20% of the control level is found at 1 × 10 −7 M. Using rat hemipituitaries and measurement of GH release by both polyacrylamide gel electrophoresis and radioimmunoassay, a maximal effect of GH-RIH was found in the first 5 min of incubation. The inhibitory effect of GH-RIH on GH release remained constant for at least 3 h. GH-RIH does not affect the basal or induced release of prolactin and luteinizing hormone nor the high K + -induced release of GH and TSH.

Summary 1 × 10 −7 M growth hormone-release inhibiting hormone (GH-RIH or somatostatin) leads to a 50% inhibition of adenosine 3′,5′-monophosphate (cyclic AMP) accumulation in anterior pituitary tissue during the first 2 min of incubation. This lowering of cyclic AMP levels is accompanied by inhibition of the release of immunoreactive growth hormone and thyrotropin. GH-RIH has also a marked inhibitory effect on the theophyline- and prostaglandin E 2 -induced accumulation of adenohypophyseal cyclic AMP.

The PGE2-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino1]-[desamino1] [descarboxy14]- and [D-Lys4]-somatostatin similarly to somatostatin, while the [descarboxy14]-somatostatin exhibits reduced activity; [D-Lys9]-somatostatin is ineffective at a higher concentration.