Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide

Karanth, Sharada; Yu, Wen H.; Walczewska, Anna; Mastronardi, Claudio A.; McCann, Samuel M.

doi:10.1073/pnas.97.4.1891

Cited by 37 publications

(48 citation statements)

References 46 publications

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“…The AA concentration measured in the AP in the present study was 300 M, an extremely high value that is in agreement with an earlier study (7) and is greater than the concentration found in the hypothalamus (21). Incubation of APs with medium containing high [K ϩ ] resulted in increased release of AA into the medium by a factor of 3 without altering tissue concentration, but the release was not dose-dependent.…”

Section: Discussionsupporting

confidence: 80%

“…In contrast to the stimulatory effect of AA on gonadotropin secretion from APs, AA had no effect on basal LHRH release from medial basal hypothalamic explants but significantly lowered NP or excitatory amino acid NMDA-stimulated LHRH release. NP or NMDA-induced LHRH release is mediated by NO, and AA acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated LHRH release by scavenging NO (21). Our current data suggest that AA has opposite effects at the hypothalamic and pituitary levels, inhibiting LHRH release in the medial basal hypothalamus and inducing gonadotropin release from the anterior pituitary.…”

Section: Discussionmentioning

confidence: 58%

“…Sodium nitroprusside (NP), which spontaneously releases NO-stimulated LHRH release and inhibition of NO release by a competitive inhibitor of NO synthase (NOS), N G -monomethyl-L-arginine (NMMA), inhibited release of LHRH (21). The results demonstrated that AA had no effect on basal release of LHRH, but blocked the release of LHRH induced by the stimulants with a minimal effective concentration of 10 Ϫ5 M. Therefore, we hypothesized that AA is a cotransmitter released with classical transmitters from synaptic vesicles that acts to reduce chemically the NO formed, thereby providing feed-forward inhibitory control over LHRH release.…”

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confidence: 99%

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Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO

Karanth

Walczewska

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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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 M), 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 .anterior pituitary gland ͉ follicle-stimulating hormone ͉ luteinizing hormone ͉ N G -monomethyl-L-arginine ͉ sodium nitroprusside A scorbic acid (AA) is a six-carbon ketolactone-synthesized from glucose (1, 2). It is an essential vitamin for humans, primates, guinea pigs, and bats, as they lack L-gulono-␥-lactone oxidase, the last enzyme involved in its synthesis from glucose (1, 3). AA is abundant in many endocrine tissues (4, 5) and plays a pivotal role in the control of adrenal and gonadal steroidogenesis (6). Several tissues in the body accumulate AA and its biologically active oxidized form, dehydroascorbic acid. The anterior pituitary gland, brain, adrenal gland, and gonads have high concentrations of AA (2, 7-10). The concentration of AA in the brain ranges between 1.1 and 1.7 mM and remains constant despite variation in AA ingestion (11,12). Intracellular AA concentration is much higher than extracellular AA concentration, and changes in neuronal activity were shown to have a profound influence on extracellular AA (13-18). AA is further concentrated in isolated nerve terminals, and synaptic vesicles concentrate AA by an active transport mechanism (19,20).Previously, we evaluated the effect of AA on basal and stimulated release of luteinizing hormone (LH)-releasing hormone (LHRH) from medial basal hypothalamic explants produced by high potassium medium and N-methyl-D-aspartic acid (NMDA). Sodium nitroprusside (NP), which spontaneously releases NO-stimulate...

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 58%

mentioning

confidence: 99%

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Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO

Karanth

Walczewska

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Similar ameliorating effects of AA against EOF were reported in transported pigs (Adenkola & Ayo 2009;Asala et al 2011) and goats (Minka & Ayo 2010b) under extreme thermal environment. The mechanism by which AA protected the erythrocytes of the rabbits from haemolysis may be through the inhibitory role of AA on corticosterone (Karanth et al 2000;Balz 2003), and its detoxifying and scavenging effects on free radicals generated during transportation (Seibert et al 2001;Urban-Chmiel et al 2009;Minka & Ayo 2010a). Besides, AA has been demonstrated to reduce the capacity of O 2 consumption through tissue oxidative metabolism and decrease heat load by enhancing mechanism of thermoregulation via increasing heat loss (Kuth & Forbes 1993), which may also decrease the generation of free radicals and further reduce lipopeoxidation.…”

Section: Post-transportation Periodmentioning

confidence: 99%

Effect of ascorbic acid administration on erythrocyte osmotic fragility in rabbits (Oryctolagus cuniculus) subjected to road transportation

Ayo

Minka

Hussein

2014

Journal of Applied Animal Research

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The physiological responses of erythrocytes of rabbits transported by road for 2 h under hot-humid climate and the ameliorating effect of ascorbic acid (AA) were investigated. Nine rabbits served as experimental (treated) and were administered AA orally at a dose of 100 mg/kg body weight, while seven other rabbits served as control and were given equivalent of sterile water only. Thirty minutes after AA administration, the rabbits were transported. The erythrocyte osmotic fragility (EOF) values recorded in the control rabbits immediately after transportation and three days posttransportation were significantly (P < 0.05) higher than the pre-transportation values and the corresponding values obtained in treated rabbits. They were indicated by an increase in haemolysis on each point of the fragility curve. The result suggested that road transportation resulted in haemolysis of erythrocytes, which lasted for three days after transportation. Thus, the rabbits may require more than three days after transportation for their erythrocytes to return to base-line values. In treated rabbits, the transportation had no significant (P > 0.05) effect on the EOF. The result demonstrated that 2 h of road transportation of rabbits under adverse climatic conditions resulted in oxidative damage of erythrocyte membrane, which was alleviated by AA administration.

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“…Therefore, by affecting the thermoregulatory centre, the antioxidant vitamins apparently exerted ameliorating effects on the elevated CT in the transported quails. Furthermore, the fact that these vitamins are known to inhibit the release of cortisol [40,42], the chief fear hormone, may be involved in the mechanism of regulation of the body responses, aimed at maintaining homeostasis. In addition, VE and AA have been reported to reduce heat load in birds [12,14,16,21,43].…”

Section: Discussionmentioning

confidence: 99%

Effects of Antioxidants Vitamin E and C on ErythrocyteFragility, HaemoglobinIndex and Colonic Temperature of Transported Japanese Quails (Coturnixcoturnix japonica)

Minka¹

2013

J Veterinar Sci Technolo

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The present study investigated the effects of antioxidants Vitamin E (VE) and C (ascorbic acid, AA) on erythrocytes osmotic fragility (EOF), haemoglobin index (HI), colonic temperature (CT) and recovery times of transported Japanese quails during the hot-dry conditions. Two hundred male Japanese quails were used. The birds were randomly and equally divided into four groups: VE and AA groups, administered with 0.5 mg/kg and 200 mg/ kg body weight of VE and AA, respectively, control transported group (control group), administered with 0.5 ml of sterile water, and sedentary non-transported group (S). One hour after the administration of the antioxidants, the birds were transported by road for 2 h. The EOF, HI and CT were recorded before transportation, immediately after transportation (0) and on 3 rd and 7 th day of post-transportation period. The results showed that transportation induced hyperthermia, increased EOF and hypochromic erythrocytes in the quails, the effects of which were mitigated by antioxidants VE and AA. Base-line values for EOF were returned to normal in the control, AA and VE quails on days 7, 3 and 0, respectively post-transportation. The findings showed that recovery time after transportation in quails should be 7 days; but the duration may be reduced to 3 days if treated with AA or eliminated completely if the quails are treated with VE before transportation. The ameliorating effect was more pronounced in quails administered with antioxidant VE. The EOF may be employed as a biomarker and additional diagnostic tool for the assessment of transport-induce oxidative stress in quails. [7,10].The use of EOF as a biomarker of road transport-induced stress in livestock is a new field of study that may add to the arsenals of tests, currently used in the diagnosis of stress due to road transportation [11][12][13]. Body temperature measurement is an important method of evaluation of physiological status. It is also an ideal indicator for the assessment of stress and adaptability of livestock, including poultry, to various environmental stress factors [14][15][16]. Effects of Antioxidants Vitamin E and C on ErythrocyteFragilitySeveral stress factors have been reported to decrease the level of body antioxidants, vitamin E (VE) and vitamin C, otherwise known as ascorbic acid (AA); resulting in increases in the body requirements in these vitamins [14,[17][18][19]. The administration of the vitamins exerts ameliorating effects which are well manifested; when the body AA and VE are either overwhelmed or exhausted as a result of increased ROS generation by stress factors that overtax the animal control systems [18,20]. Therefore, a decrease in the concentration of antioxidant vitamins causes an increase in lipid peroxidation in the plasma and tissues, leading to damage of cell membranes [21,22]. Previous reports have revealed the beneficial effects of supplementation of VE and AA on birds and animals, subjected to various oxidative stress factors [12,16,18,22].Several studies have evaluated the respon...

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Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide

Cited by 37 publications

References 46 publications

Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO

Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO

Effect of ascorbic acid administration on erythrocyte osmotic fragility in rabbits (Oryctolagus cuniculus) subjected to road transportation

Effects of Antioxidants Vitamin E and C on ErythrocyteFragility, HaemoglobinIndex and Colonic Temperature of Transported Japanese Quails (Coturnixcoturnix japonica)

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