Vitamin E, a dietary factor, is essential for reproduction in animals. It is an antioxidant present in all mammalian cells. Previously, we showed that ascorbic acid (AA) acted as an inhibitory neurotransmitter in the hypothalamus by scavenging nitric oxide (NO). Earlier studies have shown the antioxidant synergism between vitamin E and ascorbic acid (AA). Therefore, it was of interest to evaluate the effect of vitamin E on luteinizing hormone-releasing hormone (LHRH) and AA release. Medial basal hypothalami from adult male rats of the Sprague Dawley strain were incubated with Krebs-Ringer bicarbonate buffer or graded concentrations of a water soluble form of vitamin E, tocopheryl succinate polyethylene glycol 1000 (TPGS, 22–176 μM) for 1 hr. Subsequently, the tissues were incubated with vitamin E or combinations of vitamin. E + N-methyl-D-aspartic acid (NMDA), an excitatory amino acid for 30 min to study the effect of prior and continued exposure to vitamin E on NMDA-induced LHRH release. AA and LHRH released into the incubation media were determined by high-performance liquid chromatography and radioimmunoassay, respectively. Vitamin E stimulated both LHRH and AA release. The minimal effective concentrations were 22 and 88 μM, respectively. NMDA stimulated LHRH release as previously shown and this effect was not altered in the combined presence of vitamin E plus NMDA. However, AA release was significantly reduced in the combined presence of vitamin E plus NMDA. To evaluate the role of NO in vitamin E-induced LHRH and AA release, the tissues were incubated with vitamin E or combinations of vitamin E + NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NO synthase. NMMA significantly suppressed vitamin E-induced LHRH and AA release indicating a role of NO in the release of both LHRH and AA. The data suggest that vitamin E plays a role in the hypothalamic control of LHRH and AA release and that the release is mediated by NO.
Get full access to this article
View all access options for this article.
References
1.
Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science55:650, 1922.
2.
Horwit MK. Vitamin E. In: Goodhart R, Shils M, Eds. Modern Nutrition in Health and Disease (6th ed). Philadelphia: Lea and Febieger, pp181–189, 1980.
3.
Machlin LJ. In: Machlin LJ, Ed. Handbook of Vitamins: Nutritional biochemical and clinical aspects. New York: Dekker, pp245–265, 1984.
4.
Sokol RJ. Vitamin E and neurologic function in man. Free Rad Biol Med6:189–207, 1989.
5.
Lieber DC. The role of metabolism in the antioxidant function of vitamin E. Crit Rev Toxicol23:147–169, 1993.
6.
Burton GW, Ingold KU. Vitamin E as an in vitro and in vivo antioxidant. Ann New York Acad570:7–22, 1989.
7.
Ingold KU, Burton GW, Foster DO, Hughes L, Lindsay DA, Webb A. Biokinetics of and discrimination between dietary RRR and SRR-alpha-tocopherols in the male rat. Lipids22:163–172, 1987.
8.
Chow CK. Vitamin E and blood. World Rev Nutr Diet45:133–166, 1985.
9.
Bauernfeind JC, Rubin SH, Surmatis JD, Ofner A. Carotenoids and fat soluble vitamins: contribution to food, feed and pharmaceuticals. Int Z Vitamin Forsch40:391–416, 1970.
10.
Gruger EH, Tappel AL. Reactions of biological antioxidants 3. Composition of biological membranes. Lipids6:147–148, 1971.
11.
Arita M, Sato Y, Miyata A, Tanabe T, Takahashi E, Kayden HJ, Arai H, Inoue K. Human alpha-tocopherol transfer protein: cDNA cloning expression and chromosomal localization. Biochem J306:437–443, 1995.
12.
Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O, Arai H, Inoue K. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett409:105–108, 1997.
13.
Boscoboinik D, Szewczyk A, Hensey CF, Azzi A. Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C. J Biol Chem266:6188–6194, 1991.
14.
Stocker A, Zimmer S, Spycher SE, Azzi A. Identification of a novel cytosolic tocopherol binding protein: structure, specificity and tissue distribution. IUBMR Lif48:49–55, 1999.
15.
Burton GW, Ingold KU. Auto oxidation of biological molecules 1. The antioxidant activity of vitamin E and related chain breaking phenolic antioxidants in vitro. J Am Chem Soc103:6472–6477, 1981.
16.
Burton GW, Joyce A, Ingold KU. Is vitamin E the only lipid-soluble chain breaking antioxidant in human blood plasma and erythrocyte membranes? Arch Biochem Biophys221:281–290, 1983.
17.
Burton GW, Cheesman KH, Doba T, Ingold KU, Slater TF. Vitamin E as an antioxidant in vitro and in vivo. Ciba Found Sympo101:4–18, 1983.
18.
Burton GW, Ingold KU. Vitamin E: application of the principles of physical organic chemistry to the exploration of its structure and function. Acc Chem Res19:194–201, 1986.
19.
Stahl W, Sies H. Antioxidant defense: Vitamins E and C and carotenoids. Diabetes46(Suppl.2):S14–S18, 1997.
20.
Lambelet P, Saucy F, Loliger J. Radical exchange reactions between vitamin E, vitamin C and phospholipids in autooxidizing polyunsaturated lipids. Free Rad Res20:1–10, 1994.
21.
Chan AC. Partners in defense, Vitamin E and vitamin C (review). Can J Phys Pharmacol71:725–731, 1993.
22.
Beyer RE. The role of ascorbate in antioxidant protection of biomembranes: Interaction with vitamin E and coenzyme Q. J Bioenergitics Biomembr26:349–358, 1994.
23.
Traber MG, Kayden HJ, Green JB, Green MH. Absorption of water miscible forms of vitamin E in a patient with cholestatis and in thoracic duct-cannulated rats. Am J Cli Nutr44:914–923, 1986.
24.
Sokol RJ, Heubi JE, Butler-Simon N, McClung HJ, Lilly JR, Silverman A. Treatment of vitamin E deficiency during chronic childhood cholestatis with oral d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS). 1. Intestinal absorption, efficiency and safety. Gastroenterology93:975–985, 1987.
25.
Sokol RJ, Heubi JE, Iannaccone S, Bove KE, Harris RE, Ballistreri WF. The mechanism causing vitamin deficiency during chronic childhood cholestatis. Gastroenterology85:1172–1182, 1983.
26.
Gallo-Torres H. Obligatory role of bile for the intestinal absorption of vitamin E. Lipids5:379–384, 1970.
27.
Sokol RJ, Butler-Simon NA, Bettis D, Smith DJ, Silverman A. Tocopheryl polyethylene glycol 1000 succinate therapy for vitamin E deficiency during chronic childhood cholestatis: Neurologic outcome. J Pediatr111:830–836, 1987.
28.
Karanth S, Yu WH, Walczewska A, Mastronardi CA, McCann SM. Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide. Proc Natl Acad Sci USA97:1891–1896, 2000.
29.
Harapanhalli RS, Howell RW, Rao DV. Testicular and plasma ascorbic acid levels in mice following dietary intake: a high performance liquid chromatographic analysis. J Chromatogr614:233–243, 1993.
30.
Bonavera JJ, Sahu A, Kalra PS, Kalra SP. Evidence that nitric oxide may mediate the ovarian steroid induced luteinizing surge: involvement of excitatory amino acids. Endocrinology133:2481–2487, 1993.
31.
Donoso AO, Lopez FJ, Negro-Vilar A. Glutamate receptors of the non N-methyl D-aspartic acid type mediate the increase in luteinizing hormone releasing hormone release by excitatory amino acids in vitro. Endocrinology126:414–420, 1990.
32.
Bourguignon JP, Gerard A, Franchimont P. Direct activation of gonadotropin releasing hormone secretion through different receptors to neuroexcitatory amino acids. Neuroendocrinology49:402–408, 1989.
33.
Morertto M, Lopez FJ, Negro-Vilar A. Nitric oxide regulates luteinizing hormone releasing hormone secretion. Endocrinology133:2399–2402, 1993.
34.
Mahachoklertwattana P, Black SM, Kaplan SL, Bristow JD, Grumbachi MM. Nitric oxide synthesized by gonadotropin releasing hormone neurons is a mediator of n-methyl-D-aspartate (NMDA) induced GnRH secretion. Endocrinology135:1705–1712, 1994.
35.
Rettori V, Belova N, Dees WL, Nyberg CL, Gimeno M, McCann SM. Role of nitric oxide in the control of luteinizing hormone releasing hormone release in vivo and in vitro. Proc Natl Acad Sci USA90:10130–10134, 1993.
36.
Bendich A, D’Apolito P, Gabriel E, Machlin LJ. Interaction of dietary vitamin C and vitamin E on guinea pig immune responses to mitogens. J Nutr114:1588–1593, 1984.
37.
Kanazawa K, Takeuchi S, Hasegawa R, Okada M, Makiyama I, Hirosa N, Toh T, Cho SH, Kobayashi M. Influence of ascorbic acid deficiency on the level of non-protein SH compounds and vitamin E in the blood and tissues of guinea pigs. Nihon Univ J Med23:257–263, 1981.
38.
Igarashi O, Yonekawa Y, Fujiyama-Fujihara Y. Synergistic action of vitamin E and vitamin C in vivo using a new mutant of wister strain rats, ODS, unable to synthesize vitamin C. J Nutr Sci Vitaminol37:359–369, 1991.
39.
Pecker JE, Slater TF, Willson RL. Direct observation of a free radical interaction between vitamin E and vitamin C. Nature278:737–738, 1979.
40.
Niki E, Tsachiya J, Tanimura R, Kamiya T. Regeneration of vitamin E from α-chromonaxyl radical by glutathione and vitamin C. Chem Lett 789–792, 1982.
41.
Martin A, Janigian D, Shukitt-Hale B, Prior RL, Joseph JA. Effect of vitamin E intake on levels of vitamins E and C in the central nervous system and peripheral tissues: implications for health recommendations. Brain Res845:50–59, 1999.
42.
Moriguchi S, Muraga M. Vitamin and Immunity. Vit & Horms59:305–336, 2000.
43.
Coquette A, Vray B, Vanderpas J. Role of vitamin E in the protection of resident macrophage membrane against oxidative damage. Arch Int physiol Biochem94:S29–S34, 1986.
44.
Tengerdy RP, Heinzerling RH, Brown GL, Mathias MM. Enhancement of the immune response by vitamin E. Int Arch Allergy Applic Immunol44:221–232, 1973.
45.
Bendich A. Antioxidant vitamins and immune responses. In: Chandra RK, Ed. Nutrition and Immunology, pp125–148, 1988.
46.
Muller DP, Lloyd JK, Wolff OH. Vitamin E and neurological function. Lancet8318:225–228, 1983.
47.
Mehlhorn RJ, Cole G. Free radical theory of aging: A critical review. Adv Free Rad Biol Med1:165–223, 1985.
48.
Noda Y, McGeer PL, McGeer EG. Lipid peroxides in brain during aging and vitamin E deficiency: Possible relations to changes in neurotransmitter indices. Neurobiol Aging3:173–178, 1982.
49.
Meydani SN, Barklund MP, Liu S, Meydani M, Miller R, Cannon J, Morrow F, Rocklin R, Blumberg J. Vitamin E supplements enhances cell-mediated immunity in healthy elderly. Am J Clin Nutr52:557–563, 1990.
50.
Meydani SN, Meydani M, Verdon CP, Shapiro AC, Blumberg JB, Hayes KC. Vitamin E supplementation suppresses prostaglandin E2 synthesis and enhances the immune response in aged mice. Mech Age Dev34:191–201, 1986.
51.
Sakai S, Moriguchi S. Long term feeding of high vitamin E diet improves the decreased mitogen response in rat splenic lymphocytes with aging. J Nut Sci Vitaminol (Tokyo).43:113–122, 1997.
52.
Katzman R, Kawas C. The epidemiology of dementia and Alzheimer disease. In: Terry RD, Katzman R, Bick KL, Eds. Alzheimer Disease. New York: Raven Press, pp105–119, 1994.
53.
Martin RN, Harper CG, Stokes GB, Master CL. Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer’s disease may reflect oxidative stress. J Neurochem46:1042–1045, 1986.
54.
Anneren G, Gardner A, Lundin T. Increased glutathione peroxidase activity in erythrocytes in patients with Alzheimer’s disease / senile dementia of Alzheimer’s type. Acta Neurol Scand73:586–589, 1986.
55.
Tohgi H, Abe T, Nakanishi M, Hamato F, Sasaki K, Takahashi S. Concentrations of alpha-tocopherol and its quinone derivative in cerebrospinal fluid from patients with vascular dementia of the Binswanger type and Alzheimer type dementia. Neurosci Lett174:73–76, 1994.
56.
Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, Cayley AC. Plasma concentrations of vitamins A and E and carotenoids in Alzheimer’s disease. Age Aging21:91–94, 1992.
57.
Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growndon J, Cofman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol or both as treatment for Alzheimer’s disease. N Engl J Med336:1216–1222, 1997.
58.
Harding A. Vitamin E and the nervous system. Crit Rev Neurobiol3:89–103, 1987.
