Cortisol and estradiol: Nongenetic factors for hyperhomocyst(e)inemia

doi:10.1016/S0026-0495(97)90248-1

Metabolism

Volume 46, Issue 3, March 1997, Pages 247-249

https://doi.org/10.1016/S0026-0495(97)90248-1 Get rights and content

Abstract

A low plasma homocyst(e)ine concentration in premenopausal and pregnant women compared with postmenopausal women and men suggests that steroid hormones are nongenetic factors affecting homocysteine metabolism. This hypothesis was tested by determining plasma homocyst(e)ine levels in adult male rats treated with cortisol, estradiol, or a combination of both. Mean plasma homocyst(e)ine concentrations were 3.71 ± 0.71, 5.26 ± 1.76, and 4.28 ± 0.84 nmol/mL in cortisol-treated, estradiol—treated, and cortisol plus estradiol-treated groups, respectively. These values were substantially low compared with the level of 7.32 ± 0.89 nmol/mL plasma homocyst(e)ine in the control group, indicating a significant effect of steroid hormones on homocysteine metabolism.

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Cited by (53)

Prognostic Value of C-Reactive Protein and Homocysteine in Large-Artery Atherosclerotic Stroke: a Prospective Observational Study
2017, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
Most males quitted smoking after IS, which may reduce Hcy levels.34 Second, in the present study, the median age for females is 63 years, and potential protecting effects of estrogens on decreasing Hcy levels were weakened or disappeared in most of the female patients.35 Third, it is now widely recognized that folic acid-based multivitamin therapy reduces Hcy levels.
Our objective is to investigate whether C-reactive protein (CRP) and homocysteine (Hcy) levels in the acute phase of large-artery atherosclerotic stroke predict long-term functional disability and recurrent vascular events.
Patients with first-ever large-artery atherosclerotic ischemic stroke were prospectively registered in the Nanjing Stroke Registry Program between January 2012 and June 2014. Venous blood samples were collected within 2 weeks after the index stroke. Patients were followed up for 1 year. The Kaplan–Meier method was performed in survival analysis. Multiple logistic regression analysis and Cox proportional hazard model were applied to identify predictors of functional disability and recurrent vascular events, respectively.
A total of 625 eligible patients (458 males) were evaluated. During the 1-year follow-up period, 63 patients suffered recurrent vascular events. An elevated CRP level is an independent predictor of poor functional disability at 1 year (P for trend = .002), in both males (P for trend = .017) and females (P for trend = .042). Hcy showed no relationship with functional disability. No significant relationship between CRP and Hcy levels and recurrent vascular events was found in total patients in multiple models. Stratified by sex, high Hcy levels were associated with recurrent vascular events in females (P for trend = .036) but not in males.
Elevated CRP levels are associated with poor functional disability in patients with large-artery atherosclerotic stroke at 1 year, and Hcy is a relatively moderate predictor of recurrent vascular events in female patients with large-artery atherosclerotic stroke at 1 year.
Homocysteine in Pregnancy
2011, Advances in Clinical Chemistry
Citation Excerpt :
Female hormones have been inversely correlated with tHcy outside of pregnancy in both synthetic and endogenous forms. tHcy was reduced following 17 β-estradiol administration in male rats [48] and men [49]. In a randomized control trial, postmenopausal women on hormone replacement therapy were reported to have lower tHcy following 5–7 years of treatment than controls that had received no substitution treatment [50].
Genetic and environmental influences on total plasma homocysteine and coronary artery disease (CAD) risk among South Indians
2009, Clinica Chimica Acta
Hyperhomocysteinemia, a documented risk factor for CAD is highly prevalent in Indians. The rationale behind the current study is to explore the genetic and environmental causes for such high prevalence as there are limited studies in this context.
A total of 108 CAD cases and 108 controls were analyzed for tHcy and 4 folate pathway genetic polymorphisms [methylene tetrahydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine methyl transferase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and glutamate carboxypeptidase II (GCPII) C1561T] using reverse phase HPLC and PCR–RFLP methods respectively.
MTHFR 677T, MTRR 66A, GCPII 1561T, male gender, alcohol intake, smoking, diabetes, creatinine and hypertension were found to influence tHcy. After controlling for confounding factors, Hyperhomocysteinemia and two of its genetic determinants i.e. MTHFR C677T [OR: 1.96, 95% CI: 1.06–3.61] and GCP II C1561T [OR: 2.09, 95% CI: 1.09–3.97] were found to be associated with risk for CAD. Significant epistatic interactions were observed between MTHFR 677T/MTR 2756G and GCP II 1561T/MTRR 66G. Alcohol intake in subjects with MTR 2756G allele was found to inflate the risk for CAD [OR: 4.15, 95% CI: 1.35–12.69].
Hyperhomocysteinemia, C677T MTHFR and C1561T GCPII are risk factors for CAD. Potential gene — gene and gene — environment interactions indicate the need for multi-variate analyses for risk prediction.
Association of parental hyperhomocysteinemia and C677T Methylene tetrahydrofolate reductase (MTHFR) polymorphism with recurrent pregnancy loss
2009, Clinical Biochemistry
To investigate the association of parental hyperhomocysteinemia, C677T Methylene tetrahydrofolate reductase (MTHFR) polymorphism and DNA damage with recurrent pregnancy loss (RPL).
A case-control study. Reverse phase HPLC, PCR-RFLP and Cytokinesis blocked micronuclei assay were used to assess total plasma homocysteine, C677T MTHFR polymorphism and DNA damage respectively. Student t-test, ANOVA and Fisher exact test were used for statistical analysis.
Maternal [mean: 11.6 ± 5.0 versus 8.6 ± 4.2 μmol/L, odds ratio (OR): 4.48] and paternal [mean: 19.6 ± 9.5 versus 14.2 ± 7.4 μmol/L, OR: 6.92] hyperhomocysteinemia, paternal age [OR: 1.16], paternal MTHFR 677T allele [OR: 2.30] and DNA damage were found to increase the risk for RPL. DNA damage showed positive correlation with plasma homocysteine and MTHFR 677T allele.
Parental hyperhomocysteinemia, paternal age, paternal C677T MTHFR polymorphism and DNA damage are risk factors for RPL. DNA damage showed positive correlation with plasma homocysteine and MTHFR 677T allele.
Plasma homocysteine levels in cycling, pregnant, and spayed bitches
2008, Animal Reproduction Science
The aim of this study was to evaluate the physiological range of homocysteine (Hcy) exhibited by bitches during the follicular (pro-oestrus), luteal (dioestrus) and anoestrus phases of cycling animals, and in pregnant and spayed bitches. The lowest concentrations of Hcy were observed during dioestrus (3.2 ± 1.27 μmol/L) and in pregnant bitches (3.9 ± 1.72 μmol/L), and the highest concentrations during anoestrus (7.8 ± 0.6 μmol/L) and in spayed bitches (12.1 ± 5.16 μmol/L).
Epigenetic control of 11 beta-hydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension
2008, Atherosclerosis
Citation Excerpt :
DNA methylation is catalyzed by methyltransferases which use S-adenosylmethionine, a product of one-carbon metabolism, as methyl donor [16]. In a rodent experimental model [17,18], a role for glucocorticoids in affecting one-carbon metabolism has been suggested [17–19] and this pathway is known to modulate DNA methylation [16,20]. Such a possibility that cortisol thus modulates methylation of DNA at this site could be only proven by determining whether such patients show reduced HSD11B2 promoter methylation after prednisone withdrawal together with normalization of the ratio.
Lower activity of 11 beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) classically induces hypertension by leading to an altered tetrahydrocortisol- versus tetrahydrocortisone-metabolites (THFs/THE) shuttle. Recent cell culture and animal studies suggest a role for promoter methylation, a major epigenetic feature of DNA, in regulation of HSD11B2 expression. Little is known, however, of human HSD11B2 epigenetic control and its relationship with the onset of hypertension.
To explore the possible relevance of HSD11B2 promoter methylation, by examining human peripheral blood mononuclear cell (PBMC) DNA and urinary THFs/THE ratio as a biochemical indicator of 11beta-HSD2 activity, in blood pressure control.
Twenty-five essential hypertensives and 32 subjects on prednisone therapy were analyzed, the latter to investigate 11beta-HSD2 function in the development of hypertension.
Elevated HSD11B2 promoter methylation was associated with hypertension developing in glucocorticoid-treated patients in parallel with a higher urinary THFs/THE ratio. Essential hypertensives with elevated urinary THFs/THE ratio also showed higher HSD11B2 promoter methylation.
These results show a clear link between the epigenetic regulation through repression of HSD11B2 in PBMC DNA and hypertension.

View all citing articles on Scopus

^☆: Supported by research grants from Seoul National University College of Medicine Research Fund and from the National Heart, Lung, and Blood Institute (HL 36135).

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Cortisol and estradiol: Nongenetic factors for hyperhomocyst(e)inemia☆

Abstract

Atherosclerosis

Metabolism

Metabolism

Atherosclerosis

Am J Obstet Gynecol

Life Sci

Plasma homocysteine and cardiovascular disease

Hyperhomocyst(e)inemia as risk factor for occlusive vascular disease

Annu Rev Nutr

Homocyst(e)ine and arterial occlusive disease

J Intern Med

Decreased serum homocysteine in pregnancy

Eur J Clin Chem Clin Bioch

Cysteine-homocysteine mixed disulphide: Differing plasma concentrations in normal men and women

Clin Sci

Unique efficiency of methionine metabolism in premenopausal women may protect against vascular disease in the reproductive years

J Clin Invest

Protein-bound homocyst(e)ine