Handling of luteinizing hormone-releasing hormone by renal proximal tubular segments in vitro.

[pyroglutamyl-3,4-3H]Luteinizing hormone-releasing hormone (LHRH) was microperfused through isolated segments of rabbit proximal straight tubules and incubated with isolated brush border microvilli from rabbit renal tubules. About 4.8% of perfused 3H label was reabsorbed into the bathing medium per millimeter of tubule length per minute, and 1% or less of perfused label was sequestered per millimeter of nephron segment. The 3H label content of the bathing medium varied linearly with perfusion time (30 min), suggesting a constant rate of reabsorption. Analysis by high performance liquid chromatography showed that the collection fluid and brush border incubation medium contained significant amounts of labeled pGlu-His, pGlu-His-Trp, and pGlu-His-Trp-Ser, as well as LHRH, while the bathing medium contained pGlu, pGlu-His, pGlu-His-Trp-Ser, a very small amount of pGlu-His-Trp, and no LHRH. These data suggest that the partial hydrolysis of [3H]LHRH to these peptide metabolites takes place in proximal tubules through contact digestion by brush border enzymes. The metabolites and/or hormone are probably reabsorbed and broken down further within the cell to produce pGlu, which becomes an additional metabolite found in the bathing medium.