Degradation of LH-RH

Abstract

The neuropeptide Luteinizing Hormone — Releasing Hormone (LH-RH, pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂) participates in synaptic events and the hypothalamic control of adenohypophyseal hormone secretion. Since the peptide is rapidly hydrolyzed by various tissue homogenates, it has been postulated that the biological inactivation of LH-RH at the target site is catalyzed by a peptidase, which might possibly be specific for this neuropeptide. Furthermore, it has been suggested that the feedback-controlled alterations of such an enzymatic activity might be involved in the regulation of the LH-RH metabolism and thus in the control of the biological activity of this peptide (Griffiths et al., 1975; Fridkin et al., 1977; Kuhl et al., 1978; Advis et al., 1982). Alternatively, it is conceivable that LH-RH is degraded by general proteolytic enzymes, which might fulfill a scavenger function at the site of target interaction (if located in the vicinity of the receptors) or a more general metabolic clearance function at other sites. It is clear that such enzymes cannot serve a regulatory function. For answering these questions it is a prerequisite to delineate the pathway of LH-RH fragmentation and to evaluate the biochemical properties of the enzymes capable of hydrolyzing this neuropeptide.