Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO.
Because high concentrations of ascorbic acid (AA) are found in the adenohypophysis, we hypothesized that it might have an acute effect on the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the gland, particularly because we have reported that AA rapidly inhibits stimulated LH-releasing hormone (LHRH) release from medial basal hypothalamic explants. Incubation of anterior pituitary halves from adult male rats with 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. Release remained on a plateau from 10(-5) to 10(-2) M. When both AA and an effective concentration of LHRH were incubated together, there was no additive response to LHRH and the response was the same as to either compound alone. The FSH and LH release in response to AA was blocked by incubation with N(G)-monomethyl-l-arginine (NMMA) (300 microM), a competitive inhibitor of NO synthase. NMMA also inhibited LHRH-induced LH and FSH release and gonadotropin release in the presence of both LHRH and AA, whereas sodium nitroprusside, a releaser of NO, stimulated LH and FSH release. Membrane depolarization caused by incubation in high potassium (K(+) = 28 or 56 mM) medium stimulated release of FSH, LH, and AA that was blocked by NMMA. We hypothesize that AA is released with FSH and LH from secretory granules. AA is transported back into gonadotropes by the AA transporter and increases intracellular [Ca(2+)]-activating NO synthase that evokes exocytosis of gonadotropins and AA by cGMP.
Karanth
S
S
Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA.
Yu
W H
WH
Walczewska
A
A
Mastronardi
C A
CA
McCann
S M
SM
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001205:Ascorbic Acid; D011188:Potassium