Differences between in vitro and in vivo degradation of LHRH by rat brain and other organs.

Homogenates of brain, pituitary, liver, lung, ovary, and testes were incubated with [pyro Glu1-3,4-3H]luteinizing hormone-releasing hormone ([3H]LHRH), and the profiles of metabolites generated as a function of time were determined. After 5 min of incubation, 5 was the predominant metabolite in most homogenates. Although the profiles of metabolites varied at different time intervals, metabolites 2, 3, 4, and 5, and in some instances 7 and 9, appeared to form simultaneously and were detectable at 10 min.

In vivo metabolism of tritiated LHRH by the whole kidney and individual tubules of rats.

[pyroglutamyl-3,4-3H]Luteinizing hormone-releasing hormone ([3H]LHRH) and [14C]inulin were infused into individual nephrons in Inactin-anesthetized rats and the amount of radioactive label and the identity of the radioactively labeled material in urine were determined. The site of infusion was identified by latex injection and microdissection. [3H]LHRH was microinfused at 1.

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.

An approach to the elucidation of metabolic breakdown products of the luteinizing hormone-releasing hormone.

Metabolic breakdown of the luteinizing hormone-releasing hormone (LH-RH) could lead to the following fragments containing pyroglutamic acid: pyroglutamic acid (1), pGlu-His (2), pGLu-His-Trp (3), pGlu-His-Trp-Ser (4), etc., and finally pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly (10). We have synthesized fragments 2-10 and successfully separated all ten metabolites and LH-RH by high-performance liquid chromatography (HPLC) with a muBondapak C18 column.