Hormonal and bone parameters in pubertal girls.

Here we analyzed associations between muscles mass, total bone mineral content (BMC), lumbar spine bone density (BMD L1-L4) and serum or urine hormones in healthy peripubertal girls. Total BMC and areal BMD L1-L4, muscle mass and fat were measured by dual-energy X-ray absorptiometry (DXA). Muscle force (N) was estimated by a dynamometer. Circulating estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 25-hydroxy vitamin D, parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), leptin, osteocalcin, bone isoenzyme of alkaline phosphatase (bALP) and total calcium and phosphorus were quantified as the nocturnal melatonin and serotonin urinary excretion. Partial correlations adjusted for height, Tanner score and physical activity confirmed positive relationships between BMC or BMD L1-L4 (Z-score) and lean mass or fat. Furthermore, positive relationship was observed between BMC or BMD L1-L4 (Z-score) and serum leptin. After adjustment for Tanner score and physical activity, positive associations were observed between lean mass and IGF-1, leptin levels or muscle force. We proved positive relationships between bone mass and serum leptin in peripubertal girls.

Patients with IgA nephropathy have altered levels of immunomodulatory C19 steroids. Glucocorticoid therapy with addition of adrenal androgens may be the choice.

Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m(2) of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan's multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7alpha-, 7beta-, and 16alpha-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with delta(5)-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs.

Steroid hormones and homocysteine in the outcome of patients with normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7alpha-hydroxy-DHEA, 7beta-hydroxy-DHEA, 7-oxo-DHEA, 16alpha-hydroxy-DHEA (all LC-MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16alpha-hydroxy-DHEA and plasma DHEAS, 7beta-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow-up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia.

Increased serum levels of C21 steroids in female patients with multiple sclerosis.

Multiple sclerosis (MS) is one of the most common neurological diseases. This neurodegenerative autoimmune disease manifests as inflammatory and demyelinating impairment of the central nervous system (CNS). Although some studies demonstrated associations between altered steroidogenesis and pathophysiology of MS as well as the importance of steroids in the pathophysiology of MS, the knowledge concerning the steroid metabolome in female patients is limited. Hence, 51 steroids and steroid polar conjugates were measured in the serum of 12 women with MS, untreated with steroids and 6 age-corresponding female controls with the use of gas chromatography - mass spectrometry (GC-MS). The data were processed using age adjusted ANCOVA, receiver operating characteristics (ROC) analysis and orthogonal projections to latent structures (OPLS). Our data show higher levels of circulating C21 steroids including steroid modulators of ionotropic type A gamma-aminobutyric acid (GABA A) receptors and glutamate receptors. Furthermore, the levels of GABAergic androsterone and 5-androsten-3beta,7alpha,17beta-triol were also higher in the female MS patients. In conclusion, the data demonstrate higher levels of circulating C21 steroids and their polar conjugates and some bioactive C19 steroids in women with MS, which may influence neuronal activity and affect the balance between neuroprotection and excitotoxicity.

[New drugs with positive effects on bones]. / Nové látky s pozitivním úcinkem na kost.

The paper concerns the nontraditional treatment of osteoporosis using endogenous substances regulating bone metabolism, and also new drugs. NO in high concentrations decreases the activity of osteoclasts, scavenges superoxides which destroy connective tissue, and activates 1 alpha-hydroxylase in kidneys. Bone metabolism is effectively influenced by donors of NO or by modulators of NO synthase. Osteoclastic function is also inhibited by vitamin K. The administration of the vitamin is indicated in osteoporotic patients with proven vitamin K deficiency. Antiestrogens (tamoxifen), ipriflavon and analogues of wortmannin have antiresorptive activity. Under certain conditions parathyroid hormone (PTH) is anabolic for bone. The positive effect on bone was confirmed with the subcutaneous administration of small doses of PTH simulating physiologic pulsatile secretion, as well as the intact somatotropin-IGF-I (insulin like growth factor-I) axis. PTH is extremely useful, especially in osteoporosis induced by hypoestrinism. Somatotropin (GH) also has an anabolic effect on bone. The hormone stimulates bone metabolism with a prevalence of formation due to direct action on bone, as well as by means of IGF-I. Further growth factors with positive osteoprotic effect are TGF-beta (transforming growth factor-beta), FGF (fibroblast growth factor) and calcium conserving dihomogammalinoleic acid. Magnesium influences bone in different ways. It activates osteoblasts, increases bone mineralization, and enhances the sensitivity of target tissues (incl. bone) to PTH and 1,25(OH)2 vitamin D3, Under certain conditions however, magnesium can stimulate bone resorption. A more potent factor than magnesium is stroncium, which not only activates osteoblats but decreases the number of osteoclasts, thus abolishing bone resorption and enhancing formation. Bicarbonates are also favourable for bone. NaHCO3 together with potassium citrate stimulates osteoblasts and enhances bone mineralisation. In the review other prospective substances are also discussed. The osteoprotic effects of most of these factors were confirmed in vitro and in studies in animals, but their use in clinical practice is still a matter for investigation. Mutual interactions with classical osteoprotic drugs remain to be established.

The effect of epitestosterone on the plasma levels of LH and FSH in ovariectomized immature rats.

Immature ovariectomized female rats primed with estradiol or without estrogen priming were treated with epitestosterone i.p. After 7 h blood was collected and LH and FSH levels were determined. The dose-response relationship was a biphasic one. LH and less markedly FSH levels decreased under epitestosterone treatment with doses up to 10 mg, whereas at higher doses an increase of gonadotrophins was observed.