Enzymic degradation of luteinizing hormone-releasing hormone (LH-RH) by hypothalamic tissue

Synthetic luteinizing hormone-releasing hormone (LH-RH) lost both its immunore-activity and hormonal activity on incubation with hypothalamic or cerebrocortical slices or homogenates. This inactivation was shown to be due to degradation of the decapeptide by soluble enzyme(s) present in the 100,000 × g supernatant fraction of the homogenates. The supernatant derived from one rat hypothalamus was capable of destroying 1 μg of exogenous LH-RH within 5 min. The hexapeptide pGlu-His-Trp-Ser-Tyr-Gly was identified as the major radioactive breakdown product of [pGlu-3-³H] LH-RH, and tentative evidence for the formation of the tetrapeptide Leu-Arg-Pro-Gly-NH₂ was obtained by sequential electrophoresis and paper chromatography. These findings suggest that the Gly-Leu bond may be the preferred site of cleavage.