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The pathway of LH-RH degradation by two subcellular fractions (a soluble fraction and a 25 000 X g particulate fraction) of rat hypothalamus, pituitary and cerebral cortex has been studied using high performance liquid chromatography and amino acid analysis to identify the breakdown products. The primary cleavage point in the Tyr5-Gly6 bond giving [1-5] LH-RH and [6-10] LH-RH. In the presence of dithiothreitol, cleavage of LH-RH also occurred at the Pro9-Gly10 bond giving [1-9] LH-RH. The fragment [1-5] LH-RH is further degraded sequentially from the C-terminus and [1-4] LH-RH, [1-3] LH-RH, tyrosine and tryptophan were identified. The other major fragment, [6-10] LH-RH, is rapidly broken down, the only intermediate product positively identified being Arg-Pro.
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