Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration

Serova, Lidia; Maharjan, Shreekrishna; Huang, An; Sun, Dong; Kaley, Gabor; Sabban, Esther L.

doi:10.1016/j.brainres.2004.04.002

Cited by 76 publications

(58 citation statements)

References 42 publications

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“…The characteristic effects of 17␤-E2 on hyperglycemia have been noted in a previous clinical study (Colacurci et al, 1998), although the underlying mechanisms have not yet been investigated. It has been reported that 17␤-E2 elevates mRNA levels of GTPCH-I and intracellular BH4 levels in microvascular endothelial cells in the brain (Serova et al, 2004). However, the overall pattern of effects of 17␤-E2 on BH4 and GTPCH-I observed in that study seems to differ somewhat from the pattern observed in BAECs in the present study, based on differences between microvessels and muscular and elastic arteries.…”

Section: Estrogen On Endothelial Dysfunction By High Glucose 595contrasting

confidence: 91%

17β-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease

Miyazaki-Akita

Hayashi²,

Ding³

et al. 2006

J Pharmacol Exp Ther

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In postmenopausal women, the risk of diabetic cardiovascular disease drastically increases compared with that of men or premenopausal women. However, the mechanism of this phenomenon has not yet been clarified. We hypothesized that the beneficial effects of estrogen on endothelial function may be relevant to protection against hyperglycemia-induced vascular derangement. Bovine aortic endothelial cells were incubated for 72 h in the presence and absence of the physiological concentration of 17␤-estradiol (17␤-E2) under normal and highglucose conditions. The presence of 17␤-E2 significantly counteracted the reduction in basal nitric oxide production under high-glucose conditions. This finding was associated with the recovery of endothelial nitric-oxide synthase (eNOS) protein expression, tetrahydrobiopterin (BH4) levels, and the activity and gene expression of GTP cyclohydrolase I (GTPCH-I), a rate-limiting enzyme for BH4 synthesis. Both the gene transfer of estrogen receptor ␣ using adenovirus and treatment with the protein kinase C inhibitor bisindolylmaleimide I significantly enhanced the effects of 17␤-E2 treatment under high-glucose conditions, whereas these effects were abolished by the estrogen receptor antagonist ICI 182,780 (faslodex). Transfection of small-interfering RNA targeting eNOS resulted in a marked reduction in GTPCH-I mRNA under both normal and highglucose conditions, but this reduction was strongly reversed by 17␤-E2. These results suggest that the activation of ER␣ with 17␤-E2 can counteract high-glucose-induced down-regulation of eNOS and GTPCH-I in endothelial cells. Therefore, estrogen deficiency may result in an exaggeration of hyperglycemiainduced endothelial dysfunction, leading to the development of cardiovascular disease in postmenopausal diabetic women.

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Section: Estrogen On Endothelial Dysfunction By High Glucose 595contrasting

confidence: 91%

17β-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease

Miyazaki-Akita

Hayashi²,

Ding³

et al. 2006

J Pharmacol Exp Ther

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“…Circulatory estradiol levels are lower in diabetic women and rats (30,39). Estradiol-17␤ increases both nNOS expression and GTP cyclohydrolase 1 expression (43,44). The latter is a rate-limiting enzyme for the production of BH4, which is required for dimerization of nNOS (12).…”

Section: Discussionmentioning

confidence: 99%

Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum

Gangula

Maner

Micci

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

100

150

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Gangula PRR, Maner WL, Micci M-A, Garfield RE, Pasricha PJ. Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J Physiol Gastrointest Liver Physiol 292: G725-G733, 2007; doi:10.1152/ajpgi.00406.2006.-Diabetic gastroparesis is a disorder that predominantly affects women. However, the biological basis of this sex bias remains completely unknown. In this study we tested the hypothesis that a component of this effect may be mediated by the nitrergic inhibitory system of the enteric nervous system. Agematched male and female Sprague-Dawley rats were studied 8 or 12 wk after streptozotocin (55 mg/kg body wt ip)-induced sustained hyperglycemia and compared with controls. Solid gastric emptying (GE) studies were performed in all the groups. Changes in gastric antrum neuronal nitric oxide synthase (nNOS) mRNA and protein levels were analyzed by real-time PCR and Western immunoblotting, respectively. nNOS dimerization studies were performed using lowtemperature SDS-PAGE. In vitro nitrergic relaxation (area under curve/mg tissue wt) was studied after the application of electric field stimulation in an organ bath. Changes in intragastric pressure (mmHg⅐s) in freely moving rats in the presence or absence of N Gnitro-L-arginine methyl ester (nitric oxide synthase inhibitor) were examined by an ambulatory telemetric method. After diabetes induction, GE is delayed in both male and female rats. However, diabetic females exhibited significant delayed GE than in diabetic males. Compared with male controls, gastric nNOS expression and nitrergic relaxation were substantially elevated in healthy female control rats, accompanied by significantly reduced intragastric pressure. The active dimeric form and dimer-to-monomer ratio of nNOS␣ were also higher in healthy females compared with male rats (P Ͻ 0.05). Diabetic females, but not males, showed significant (P Ͻ 0.05) impairment in both gastric nNOS␣ dimerization and nitrergic relaxation, accompanied by an increase in intragastric pressure. Our data provide evidence that females may have a greater dependency on the nitrergic mechanisms in health. Furthermore, diabetes seems to affect the nitrergic system to a greater extent in females than in males. Together, these changes may account for the greater vulnerability of females to diabetic gastric dysfunction.solid gastric emptying; nitrergic relaxation; intragastric pressure GASTRIC DYSMOTILITY OR GASTROPATHY occurs in 20 -55% of patients with Type 1 (insulin dependent) and up to 30% of patients with Type 2 diabetes (non-insulin dependent) (37). Symptoms of diabetic gastropathy can range from mild dyspepsia to recurrent vomiting and abdominal pain and are often associated with delayed or accelerated gastric emptying. Fundic tone abnormalities and/or poor antroduodenal coordination has been reported in diabetic patients (28). Although the pathogenesis of diabetic gastropathy is not completely understood, it appears to be much more common (up to four times) in w...

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“…These adaptive mechanisms include increased synthesis, metabolism, and release of DA per impulse, which restore functionality in the partially damaged NSDA system. Circulating estradiol can promote all these parameters, as well as behavioral recovery after 6-OHDA-induced lesions in female rodents, but fails to do so in males (McDermott et al, 1994;Pasqualini et al, 1995;Becker, 1999;Ohtani et al, 2001;Serova et al, 2004;Dluzen, 2005;Tamá s et al, 2005). It is also known that striatal interneurons, including the MSNs, undergo synaptic reorganization after 6-OHDA-induced injury to the NSDA system (Salin et al, 2009).…”

Section: Gonadal Factors Are Protective In Female But Not In Male Ementioning

confidence: 99%

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration

Cited by 76 publications

References 42 publications

17β-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease

17β-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease

Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

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