Jaroslava Tallová

Serum Concentrations of Some Neuroactive Steroids in Women Suffering from Mixed Anxiety-Depressive Disorder

Concentrations of neurosteroids may be influenced by some physiological or pathological factors. We investigated neuroactive steroids in the serum of women suffering from anxiety-depressive disorder treated with fluoxetine and in a control group, in both the follicular and the luteal phases of the menstrual cycle. Two groups of neuroactive steroids were measured by radioimmunoassays: 1) the positive allosteric modulator of GABAA receptors, allopregnanolone with its precursor progesterone and 2) pregnenolone sulfate and dehydroepiandrosterone sulfate (DHEAS) acting on GABAA receptors by an opposite mechanism. Significantly higher levels of pregnenolone sulfate (p < 0.0001) were found in patients in both phases of the menstrual cycle. Significantly higher values were recorded in pregnenolone (p < 0.001) and 17α-hydroxy-pregnenolone (p < 0.01) levels in the patients group in the follicular phase. Our results indicate that imbalance in neuroactive steroids may play a negative role in origin and course of psychiatric and neurological disorders.

Plasma levels of 7-hydroxylated dehydroepiandrosterone (DHEA) metabolites and selected amino-thiols as discriminatory tools of Alzheimer's disease and vascular dementia.

Abstract Objective: The early differential diagnosis of Alzheimers disease (AD) remains still problematic. We developed a laboratory test enabling us to distinguish patients with AD from those with vascular dementia (VD) and healthy subjects. Methods: The AD group consisted of 22 women and 18 men. The VD group consisted of 16 women and 8 men. Age-matched controls consisted of 12 women and 9 men. Plasma pregnenolone sulfate (PregS), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) were determined by radioimmunoassay. 17-Hydroxypregnenolone (17 Preg) and 7-hydroxylated metabolites of DHEA (7αDHEA, 7βDHEA) were determined by radioimmunoassay after separation by high performance liquid chromatography (HPLC). Homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cysgly) and glutathione (GSH) were measured by HPLC. Results: The ANOVA results of significant between-group differences were as follows: The PregS and the 17-Preg and DHEAS levels were independent from the diagnosis. The 7αDHEA levels significantly depended on the sex (p<0.05) and diagnosis (p<0.01). Aminothiols were influenced by the diagnosis (p<0.01, p=0.0541, p<0.01 and p=0.0536 for Cys, Hcy, Cysgly and GSH, respectively). Using a stepwise backward regression analysis, the following parameters were obtained: X=11.5+4.03×sex+1.09× Hcy+0.190 × PregS−4.76×DHEAS+3.00×DHEA− 34.3×7αDHEA−0.885× Cysgly from which P-value as a discriminator was calculated according to the formula: P=1/(1+e−x). Then, for P>0.5, a subject was considered as AD-positive (with 89% correct prediction). Discussion: The opportunity of early differential diagnosis of AD should help physicians to use suitable treatment for retardation of pathological processes.

Plasma thiols and androgen levels in polycystic ovary syndrome.

Abstract Homocysteine is a risk factor for ischemic heart disease; similarly as is hyperlipidemia or insulin resistance, which frequently occur in women with polycystic ovary syndrome. We examined the relationships between thiols and hormonal status or insulin resistance in 40 women (aged 25.8±7 years) with polycystic ovary syndrome and in 11 controls (33±5 years). Blood levels of homocysteine, glutathione, total and high density lipoprotein (HDL)-cholesterol, triglycerides, insulin, sex hormone-binding globulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, and estradiol were determined. Students t test and Spearman correlations were computed after adjustment for body mass index (BMI) and age. Homocysteine was significantly higher in polycystic ovary syndrome patients than in the control group (10.3±2.87 vs. 8.78±2.75 μmol/l; p < 0.05). In women with polycystic ovary syndrome, there were significant positive correlations between homocysteine and androstenedione (r = 0.329; p < 0.05) and glutathione and dehydroepiandrosterone sulfate (DHEA-S) (r = 0.469; p < 0.05). We conclude that homocysteine is increased in women with polycystic ovary syndrome and is probably linked to androgen levels but not to markers of insulin resistance or with lipid metabolism.

Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.

Abstract Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms of psychiatric disorders and atherogenic changes in lipid metabolism. Recent studies suggest that some neuroactive steroids and homocysteine are involved in the pathophysiology of both disorders. Homocysteine metabolism may be affected by some steroids. We were interested if the treatment of hypothyroidism would affect the above factors. We studied plasma concentrations of allopregnanolone, pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone, estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month treatment with levothyroxine. Steroids and thyroid function were monitored by measuring thyrotropin, free triiodothyronine, free thyroxine and levels of thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found that with the restoration of the thyrotropin level, free triiodothyronine, free thyroxine and homocysteine levels decreased, but the levels of steroids were not significantly altered. Steroid concentrations correlated negatively with the level of thyroid antimicrosomal antibodies.

Allopregnanolone, pregnenolone sulfate, and epitestosterone in breast cyst fluid.

The risk of breast cancer is 2 to 5 times higher in patients suffering from gross cystic disease. Breast cysts are categorized into two groups (type I and type II) according to the concentration of electrolytes in the cyst fluid. The two types also differ with respect to accumulation of steroids and steroidogenic enzyme activity. In type I cysts a higher risk of breast carcinoma could be expected. Here, we studied a possible relationship between the type of cyst and levels of epitestosterone (an endogenous antiandrogen), allopregnanolone (a product of 5alpha-reductase activity), and pregnenolone-sulfate (an activator of N-methyl-D-asparate receptors). We have found five times higher levels of epitestosterone in BCF in comparison with the circulation. Allopregnanolone levels were similar to those in plasma of women in the luteal phase of the menstrual cycle. Pregnenolone-sulfate levels in BCF were about two orders of magnitude higher when compared with the circulation. No differences were found in concentrations of the steroids studied between the types of cysts.

Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation.

Abstract Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5–6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased. Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol. As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.

Homocysteine in breast cyst fluid

Background Elevated plasma homocysteine concentrations have been reported in a variety of carcinoma, including those of the breast. The risk of breast cancer is higher in patients suffering from gross cystic disease. The breast cyst fluid contains unusual amounts of low‐ and high‐ molecular substances, including steroid hormones and their conjugates. The present study was undertaken to find out the presence of homocysteine in the fluid filling the cysts and have its concentration compared with other thiols, levels of Na+/K+ ratio and steroid hormones.

Homocysteine during the menstrual cycle in depressive women

Background Two possible factors that may have a causal relation with both depressive disorder and cardiovascular disease are elevated homocysteine and steroid hormones. Our previous study found significant changes in the plasma homocysteine concentration during the menstrual cycle in healthy women. The purpose of this study therefore was to test homocysteine in depressive women treated with fluoxetine during the menstrual cycle.

Intraindividual variability of homocysteine and related thiols concentrations in follicular fluid

PurposeTo determine intraindividual variability in concentrations of homocysteine and related thiols in follicular fluids of particular follicles after ovarian stimulation and assess the differences between follicles with/or without oocytes.MethodsHPLC-FD analysis of plasma and follicular fluid cysteine, homocysteine, cysteinylglycine and glutathione in women undergoing IVF.ResultsIn blood plasma, the homocysteine, cysteine, and cysteinylglycine concentrations decreased significantly during stimulation with rec FSH (p < 0.001). We found significant differences in concentrations of cysteine and glutathione between follicles with or without retrieved oocytes. High intraindividual variability in concentrations of thiols was determined.ConclusionsThe concentration variability of thiols between single follicles is very high and we recommend mean at least from 3 follicles with/or without oocytes for characterization of each woman. It is the best to examine individual follicles for further research and analysis of fertility outcomes.

Aminothiols in human brain tumors.

Abstract Background: Aminothiols are sulfur-containing amino acids involved in methionine metabolism. Changes in their levels play negative roles in the genesis of many diseases. These mechanisms involve direct toxicity, either on glutamate neurotransmitter receptors or cerebrovascular endothelium, and have an indirect inhibitory effect on transmethylation reactions. Oxidative stress and excitotoxicity are factors that may rise as a consequence of increased homocysteine levels in brain tissues. We discovered new information concerning concentrations of the main aminothiols in human neoplastic brain tissues. Methods: The cytosolic fractions of 73 tissue samples from human brain tumors were used for the determination of total homocysteine, total cysteine and methionine levels. Gas chromatography with flame ionization detection after reduction of disulfide bonds was the method used. Results: Average concentrations of the aminothiols examined were as follows: total homocysteine, 0.58–1.51nmol/mg; methionine, 1.16–2.07nmol/mg; and total cysteine 5.08–7.82nmol/mg of total protein. Significantly higher levels of total homocysteine were found in pituitary adenoma and glioblastoma multiforme compared with other types of tumors. Methionine and cysteine concentrations did not differ significantly according to diagnosis. Conclusions: This is the first work concerning the concentrations of aminothiols in brain tissues. The results obtained indicate the metabolic pathways that are involved in tumor formation and/or its progress, including the toxic effects of homocysteine. Clin Chem Lab Med 2006;44:978–82.