Ascorbic acid stimulates gonadotropin release by autocrine action by meansof NO

Because high concentrations of ascorbic acid (AA) are found in the adenohyp ophysis, we hypothesized that it might have an acute effect on the secretio n of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from t he gland, particularly because we have reported that AA rapidly inhibits st imulated LH-releasing hormone (LHRH) release from medial basal hypothalamic explants. Incubation of anterior pituitary halves from adult male rats wit h graded concentrations of AA for 1 h induced highly significant release of both FSH and LH with a minimal effective concentration of 10(-5) M. Releas e remained on a plateau from 10(-5) to 10(-2) M. When both AA and an effect ive concentration of LHRH were incubated together, there was no additive re sponse to LHRH and the response was the same as to either compound alone. T he FSH and LH release in response to AA was blocked by incubation with N-G- monomethyl-L-arginine (NMMA) (300 muM), a competitive inhibitor of NO synth ase. NMMA also inhibited LHRH-induced LH and FSH release and gonadotropin r elease in the presence of both LHRH and AA, whereas sodium nitroprusside, a releaser of NO, stimulated LH and FSH release. Membrane depolarization cau sed by incubation in high potassium (K+ = 28 or 56 mM) medium stimulated re lease of FSH, LH, and AA that was blocked by NMMA. We hypothesize that AA i s released with FSH and LH from secretory granules. AA is transported back into gonadotropes by the AA transporter and increases intracellular [Ca2+]- activating NO synthase that evokes exocytosis of gonadotropins and AA by cG MP.