Ascorbic acid is frequently used in in vitro studies of neurotransmitter-evoked release of luteinizing hormone-releasing hormone (LHRH) from hypothalamic fragments. Although it is assumed that ascorbate merely prevents the oxidative degradation of catecholamines, we have discovered that ascorbic acid itself produces significant increases in the release of LHRH. Our studies showed that ascorbic acid, at concentrations below 1 mM, produced a dose-dependent release of LHRH from incubated rat mediobasal hypothalamus (MBH). The magnitude of the ascorbate-induced release was in the range of 100-200% above controls; significant amounts of LHRH were released only if the MBH were incubated with ascorbate for time periods longer than 30 minutes. We also found that ascorbate-induced increases in LHRH were equivalent to those produced by another LHRH secretagogue, naloxone, and that the combined effects of the two substances were additive in nature. Although the mechanisms underlying this effect are not fully understood, nonspecific chemical reduction is probably not a factor since sodium metabisulfite did not induce the release of LHRH. It seems probable that ascorbate may enhance the activity of endogenous norepinephrine in the MBH and, thereby, lead to increased release of LHRH.
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