Beer consumption negatively regulates hormonal reproductive status and reduces apoptosis in Leydig cells in peripubertal rats.

Beer is one of the most popular alcoholic beverages consumed by young people. Ethanol intake is associated with harmful effects to the reproductive system. Bioactive compounds present in beer may diminish the toxics effect of ethanol. However, there is still little knowledge about the effect of beer consumption on hormonal regulation of male reproduction in organisms exposed to alcohol after the peripubertal age. Therefore, the aim of this study was to determine the influence of beer intake on plasma reproductive hormones, immunolocalization of cleaved caspase-3 (casp-3), and the level of the neuronal isoform of nitric oxide synthase (nNOS) in Leydig cells (LCs) in adolescent male Wistar rats. The animals, beginning at the age of 30 days, drank beer (10% ethanol; B2 group [2 weeks' exposure] and B4 group [4 weeks' exposure]), 10% ethanol solution (CE2 group [2 weeks' exposure] and CE4 group [4 weeks' exposure]), or water (C2 group [2 weeks' exposure] and C4 group [4 weeks' exposure]). Rats drinking beer for 4 weeks showed higher phenolic acid intake compared to rats drinking beer for 2 weeks. Rats exposed to beer for 4 weeks showed decreased plasma levels of follicle-stimulating hormone (FSH) and 17ß-estradiol (E2) (3.173 ng/mL and 11.49 pg/mL, respectively), compared to the CE4 (5.293 ng/mL and 43.912 pg/mL, respectively) and the C4 groups (5.002 ng/mL and 41.121 pg mL, respectively). Expression of cleaved caspase-3 in LCs was lower in the B4 group rats, compared to the CE4 group rats (ID score: 1.676 vs. 2.190). No changes in nNOS expression were observed. Beer consumption revealed a similar negative effect on hormonal regulation of male reproductive function, but lower apoptosis in LCs may be beneficial for steroidogenic activity.

Plasma adiponectin array in women with Alzheimer's disease.

Introduction Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Typical features of AD include memory loss, social dysfunction and physical impairment. Although the pathological findings in the central nervous system are well established, the etiological factors are poorly known. Recent studies suggested the role of metabolic disturbances in the development of AD neurodegeneration. Adiponectin, an anti-inflammatory and metabolism regulating factor, was linked to AD. Aim The aim was to examine whether adiponectin fractions combined with insulin/insulin resistance-associated metabolic parameters correlate with AD progression. Material and methods The study comprised 98 women: 27 with moderate to severe AD, 31 with AD at early stage and 40 healthy controls, matched for age and BMI. To evaluate memory impairment, the MMSE was performed. Plasma total adiponectin and its high-, medium- and low molecular weights were measured with ELISA. Anthropometric, clinical and metabolic parameters were assessed. Correlations between adiponectin array and measured parameters were evaluated. Results In comparison to the controls, enhanced levels of total and medium molecular weight adiponectin characterized AD individuals. In AD, we found correlations between adiponectin array, and anthropometric and biochemical parameters. After adjustment to BMI, a significant increase of the total adiponectin and high- and medium molecular weight fractions was observed. A negative correlation between low molecular weight adiponectin and MMSE was found. Conclusions Our results indicate a possible link between adiponectin variations and AD. We hypothesize that changes in adiponectin profile observed in AD result from compensatory mechanism against neuropathological processes, as well as from adiponectin homeostasis impairment.

Intracellular mechanisms involved in copper-gonadotropin-releasing hormone (Cu-GnRH) complex-induced cAMP/PKA signaling in female rat anterior pituitary cells in vitro.

The copper-gonadotropin-releasing hormone molecule (Cu-GnRH) is a GnRH analog, which preserves its amino acid sequence, but which contains a Cu(2+) ion stably bound to the nitrogen atoms including that of the imidazole ring of Histidine(2). A previous report indicated that Cu-GnRH was able to activate cAMP/PKA signaling in anterior pituitary cells in vitro, but raised the question of which intracellular mechanism(s) mediated the Cu-GnRH-induced cAMP synthesis in gonadotropes. To investigate this mechanism, in the present study, female rat anterior pituitary cells in vitro were pretreated with 0.1 µM antide, a GnRH antagonist; 0.1 µM cetrorelix, a GnRH receptor antagonist; 0.1 µM PACAP6-38, a PAC-1 receptor antagonist; 2 µM GF109203X, a protein kinase C inhibitor; 50 mM PMA, a protein kinase C activator; the protein kinase A inhibitors H89 (30 µM) and KT5720 (60 nM); factors affecting intracellular calcium activity: 2.5 mM EGTA; 2 µM thapsigargin; 5 µM A23187, a Ca(2+) ionophore; or 10 µg/ml cycloheximide, a protein synthesis inhibitor. After one of the above pretreatments, cells were incubated in the presence of 0.1 µM Cu-GnRH for 0.5, 1, and 3 h. Radioimmunoassay analysis of cAMP confirmed the functional link between Cu-GnRH stimulation and cAMP/PKA signal transduction in rat anterior pituitary cells, demonstrating increased intracellular cAMP, which was reduced in the presence of specific PKA inhibitors. The stimulatory effect of Cu-GnRH on cAMP production was partly dependent on GnRH receptor activation. In addition, an indirect and Ca(2+)-dependent mechanism might be involved in intracellular adenylate cyclase stimulation. Neither activation of protein kinase C nor new protein synthesis was involved in the Cu-GnRH-induced increase of cAMP in the rat anterior pituitary primary cultures. Presented data indicate that conformational changes of GnRH molecule resulting from cooper ion coordination affect specific pharmacological properties of Cu-GnRH molecule including specific pattern of intracellular activity induced by complex in anterior pituitary cells in vitro.

Assessment of plasma brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) concentrations in treatment-naïve humans with multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by coexisting processes of inflammation, demyelination, axonal neurodegeneration and gliosis. Autoimmune processes play a pivotal role in the disease. The immune system may be modulated by neurotrophins and neurotrophin factors. Aim of the study was to assess plasma levels of brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) in treatment-naïve humans with newly diagnosed multiple sclerosis. We also elucidated the potential influence of selected inflammatory agents on peripheral concentration of BDNF and ADNP. MATERIAL AND METHODS: The study population comprised of 31 untreated patients with MS and 36 controls from a single hospital centre. Assessment of BDNF and ADNP was performed with use of ELISA methods. VIP was measured with RIA. Selected cytokine levels (IL 6, IL 10, and TNF α) were evaluated with ELISA tests. Statistical analyses were performed. RESULTS: We failed to find any significant differences between ADNP, BDNF, VIP, CRP levels and concentration of cytokines between individuals with MS and the controls. No correlation was observed between ADNP, BDNF and VIP as the first parameter and CRP, IL 6, IL 10, TNFα levels and the Expanded Disability Status Scale score in MS. CONCLUSIONS: Newly diagnosed, treatment-naïve patients with MS have comparable levels of plasma BDNF, ADNP and VIP to those of healthy controls.

Plasma leptin levels and free leptin index in women with Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by irreversible and progressive loss of memory and other cognitive functions. Controversies still exist on the precise mechanisms contributing to neurodegeneration. Obesity and disturbances in metabolic homeostasis are thought to be AD risk factors. Adipokine leptin has receptors in the brain, also in the regions related to AD. Leptin may protect against AD. The aim was to assess leptin and soluble leptin receptor levels in plasma as well as free leptin index (FLI) in correlation with metabolic status of women diagnosed with Alzheimer's disease. Eighteen women with moderate to severe stage of AD, 40 women with AD at early stage, and 42 female controls, matched for age and body mass index, participated in the study. Leptin and soluble leptin receptor levels were measured with RIA and IRMA, respectively. Then, FLI was calculated. In addition, metabolic parameters (lipid profile, glucose and insulin concentrations, HOMA-IR) were estimated. Clinical and anthropometric data were collected. The Mini-Mental State Examination (MMSE) as a cognitive impairment measurement was performed. Correlations with both leptin and FLI, and MMSE, clinical and biochemical parameters were evaluated. Leptin levels and FLI were significantly lower and leptin receptor concentrations were higher in AD subjects when compared with the controls. In AD group leptin, soluble leptin receptor and FLI correlated with selected metabolic parameters but not with MMSE. We conclude that alterations in leptin, leptin receptor, and FLI were the most intensified in advanced AD. However, these results did not correlate with dementia stage measured with MMSE. Therefore, further intensive research is needed to explain the mechanisms involved in this phenomenon.

Association of copeptin and cortisol in newly diagnosed multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Obesity may increase the risk of developing MS. The aim of this study was to evaluate copeptin and cortisol plasma levels in newly diagnosed untreated MS patients and to determine whether copeptin and cortisol are related to the patients' clinical statuses. We report that copeptin and cortisol were higher in overweight/obese MS patients. Positive correlations were observed between the two parameters. We conclude that alterations of copeptin and cortisol levels in multiple sclerosis patients may be related to adiposity. An increase in cortisol may also be associated with copeptin secretion.

Decreased endothelin-1 plasma levels in multiple sclerosis patients: a possible factor of vascular dysregulation?

BACKGROUND: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most potent and long-lasting mediator. Vascular dysregulation can play an important role in the pathogenesis of some eye disorders and it has been hypothesized that it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS. MATERIAL AND METHODS: The MS group consisted of 39 patients (9 males, 30 females), mean age: 38.8 ± 10.02 years, range: 22-62. The control group consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4 ± 10.88 years, range: 20-62; clinically, in a non-active stage of the disease. ET-1 plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological Laboratories Co., Japan). Statistical analysis was performed with the nonparametric Mann-Whitney U test for independent groups. RESULTS: Endothelin-1 (ET-1) plasma levels were significantly lower in MS patients compared to healthy controls: mean value 0.55 ± 0.44 pg/ml (146.05 ± 118.27 fmol/ml) vs. 0.95 ± 0.48 pg/ml (252.83 ± 127.16 fmol/ml); P=0.012. CONCLUSIONS: Significantly decreased ET-1 plasma levels in the MS patients could reflect the non-active disease at the time of ET-1 measurements or the effects of immunomodulatory treatment, but it cannot be excluded that decreased ET-1 plasma levels in these patients might result from vascular dysregulation.

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17ß-oestradiol (E2) (3×20 µg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17ß-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo.

The effect of red wine consumption on hormonal reproductive parameters and total antioxidant status in young adult male rats.

Very little is known about the effects of red wine consumption on male reproductive functions. Here we report the effect of regular drinking of different types of red wine on hormonal reproductive parameters and total antioxidant status in young adult male rats. Dry red wine (D-RW) exerted higher antioxidant activity and was characterized by higher concentration of phenolic compounds compared to semi-dry (SD-RW), sweet (S-RW) and semi-sweet (SS-RW) wines. No differences in total antioxidant status of rat plasma after six weeks of drinking of the wines were detected. Increased plasma follicle-stimulating hormone levels in S-RW versus control and D-RW (5.26 vs. 3.06 and 3.21 ng mL(-1)) groups were found. The plasma testosterone concentration was lower in D-RW compared to control, SD-RW, S-RW and SS-RW groups (0.25 vs. 1.12, 1.09, 1.54 and 1.25 ng mL(-1)). Higher plasma 17ß-estradiol level in S-RW versus SD-RW and SS-RW (10.94 vs. 7.18 and 6.72 pg mL(-1)) group was stated. The prolactin level was higher in plasma of S-RW versus D-RW and SS-RW (17.35 vs. 9.74 and 8.59 ng mL(-1)) rats. The effects of red wine drinking on the hormonal regulation of the male reproductive system depend on the type and the dose of red wine. Chemical compounds naturally occurring in red wines (i.e. phenolics) may modulate the effects of ethyl alcohol, but also directly affect the male reproduction.

Plasma chemerin levels in patients with multiple sclerosis.

OBJECTIVES: Chemerin, a novel adipokine produced by adipose tissue and liver, is associated with markers of metabolic syndrome, and additionally, acting as chemoattractant for cells of immune system it may regulate immune cell properties. MATERIAL AND METHODS: In order to evaluate plasma chemerin concentration in multiple sclerosis (MS) individuals we investigated 39 MS patients (among them 23 subjects were lean and 16 were overweight or obese) and 42 controls with tension headaches (29 of them were lean and 13 were overweight or obese). All patients had a brain MRI scan with gadolinium contrast as well as an assessment of the presence of oligoclonal bands in cerebrospinal fluid (CSF) and estimation of the CSF IgG index. The neurologic status was evaluated with use of the Expanded Disability Status Scale. Chemerin levels in plasma were measured using ELISA kit. Lipid profile, glucose and insulin levels, CRP and selected cytokine concentrations were also determined. RESULTS: Plasma chemerin concentrations in overweight/obese MS subjects were higher when comparing to lean MS individuals and the controls, both from lean and overweight/obese subgroups. Significant difference was found between the results of overweight/obese MS and lean controls. CONCLUSIONS: An increase of chemerin levels in patients with multiple sclerosis is associated with overweight and obesity.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) in humans with multiple sclerosis.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system that leads to demyelination and neurodegeneration. VIP and PACAP are structurally related neuropeptides with neuroprotective and anti-inflammatory activities. To evaluate VIP and PACAP-38 in plasma and CSF in humans in correlation with IL-6, IL-10 and TNFα, we compared 20 MS individuals with 27 healthy controls. In MS, a decrease in PACAP-38 in CSF and a decrease in plasma IL-6 concentration were seen. A positive correlation between plasma VIP and plasma IL-6 was identified. We conclude that VIP and PACAP may influence the course of MS.

The effect of valproate (VPA) treatment on inositol phosphates (IPs) accumulation in non-stimulated and GnRH-treated female rat anterior pituitary cells in vitro.

OBJECTIVE: Mechanism(s) responsible for VPA-induced effects on reproductive axis activity are not fully recognized. Previously we reported that VPA suppressed only GnRH-stimulated but not the basal LH release from rat anterior pituitary (AP) cells in vitro. Since the inhibitory effect of VPA was exerted only in GnRH-activated cells, potential VPA impact on GnRH-R-coupled IP3/PKC signaling could not be excluded. In this study the effect of VPA on IPs synthesis in non-stimulated and GnRH-treated rat AP cells was examined. MATERIAL AND METHODS: In the first experiment 5 × 105 cells/ml were incubated for 3h with VPA (10 nM-10 µM), PMA (100 nM), GnRH (100 nM), PMA (100 nM) + VPA (10 nM-10 µM), GnRH (100 nM) + VPA (10 nM-10 µM). In the second experiment cells were preincubated for 24h with 1µCi myo-[23 H]-inositol, then for 30 min with 10 mM LiCl and finally for 3hr with GnRH (100 nM) VPA (1 µM, 10 µM), GnRH (100 nM) + VPA (1 µM, 10 µM). LH concentration was measured by RIA and intracellular IPs accumulation by ion-exchange chromatography analysis. RESULTS: VPA diminished GnRH-stimulated LH release without affecting PMA-induced LH release at any dose tested. Moreover, VPA-induced increase of IPs accumulation occurred in both non-stimulated and GnRH-treated cells and intensity of cellular response was similar in both groups. CONCLUSION: VPA affects IP3/PKC pathway activity through its up-regulatory effect on IPs synthesis in AP cells. VPA-induced inhibition of GnRH-stimulated LH release from gonadotrope cells appears to be the result of still unrecognized cellular mechanism.

Plasma NPY concentrations in women with acute ischemic stroke.

OBJECTIVE: It has been reported that plasma NPY levels were increased in obesity, type 2 diabetes mellitus and hypertension. The symptoms of metabolic syndrome frequently appear in patients with acute ischemic stroke. The association between plasma NPY levels and metabolic markers in women with acute ischemic stroke was investigated in the current study. METHODS: Plasma NPY concentrations were determined using radioimmunoassay in 58 women aged 60-85 (mean age: 76.5±0.8) with acute ischemic stroke and in 24 women aged 63-67 (mean age: 65.6±0.6) of the control group. Stroke was defined according to the NIHSS (National Institute of Health Stroke Scale) and was confirmed using CT or MR scan. RESULTS: The prevalence of type 2 diabetes, hypertension and insulin resistance was higher in the group of patients with stroke. Plasma NPY levels measured during the 1st day and 10 days after the acute phase of stroke were significantly lower (p<0.001) compared to the control group. CONCLUSION: In women with acute ischemic stroke plasma NPY concentrations were decreased in spite of higher frequency of the occurrence of the symptoms of metabolic syndrome.

Assessment of adiponectin and its isoforms in Polish centenarians.

BACKGROUND: The physiological mechanisms that promote longevity remain unclear. It has been suggested that insulin sensitivity is preserved in centenarians, whereas typical aging is accompanied by increasing insulin resistance. The oldest-old individuals display raised total adiponectin levels, despite the potential correlation between enhanced adiponectin and all-cause and cardiovascular mortality. AIM: To evaluate the level of adiponectin and its isoforms in sera of centenarians and to assess associations between adiponectin and metabolic parameters. PARTICIPANTS: A group of 58 Polish centenarians (50 women and 8 men, mean age 101±1.34 years) and 68 elderly persons (55 women and 13 men, mean age 70±5.69 years) as controls. MEASUREMENTS: Serum samples were analyzed to evaluate the following parameters: adiponectin array (total adiponectin, HWM-, MMW- and LMW-adiponectin; all by ELISA methods), insulin (by IRMA methods), glucose and lipid profiles. HOMA-IR was calculated. Clinical data were collected. Statistical analyses were performed. RESULTS: The concentrations of all adiponectin isoforms were significantly higher in the oldest-old participants. In the centenarian group, total adiponectin positively correlated with age and HDL-cholesterol, and HMW-adiponectin was negatively associated with insulin and triglycerides. The long-lived participants had a lower incidence of hypertension, type 2 diabetes, overweight and obesity, with lower concentrations of serum glucose and insulin, and reduced HOMA-IR. CONCLUSION: Our findings support the thesis that centenarians possess a different adiponectin isoform pattern and have a favorable metabolic phenotype in comparison with elderly individuals. However, additional work is necessary to understand the relevance of these findings to longevity.

Resistin levels in women with ischemic stroke.

OBJECTIVES: Resistin may be an independent inflammatory marker of atherosclerosis. Therefore, its circulating level might be important prognostic factor of cardiovascular disease in humans. We aimed in this study to assess plasma resistin concentration in Polish women with acute ischemic stroke, who additionally suffer from chronic diseases: diabetes, hypertension and/or obesity. The changes of resistin levels after 10 days from the onset of stroke and possible associations between resistin and pro-inflammatory cytokine TNFα were also evaluated. MATERIAL AND METHODS: Material consisted of 41 women with ischemic stroke (aged 60-85 years) and 64 controls (aged 60-85 years). Circulating resistin and TNFα concentrations were measured using ELISA. Blood was taken twice in the stroke group, in the first and tenth day from the onset of clinical symptoms, and only once in the controls. Clinical and biochemical data (blood pressure, weight, height, glucose, insulin, lipid profile) were collected. RESULTS: Higher concentrations of resistin and TNFα were observed in ischemic stroke patients at the first day comparing to the controls. Second evaluation after 10 days in comparison with the first measurement revealed significantly higher TNFα levels and non-significant lower values of resistin. Resistin positively correlated with TNFα and stroke severity. CONCLUSIONS: Changes in resistin and TNFα concentrations were observed in the course of stroke. Further investigations are required to assess the implication of these findings. Higher resistin concentration might be associated with worse neurological deficits.

The evaluation of estradiol and leptin action on the activity of the somatotropic and gonadotropic axes in peripubertal female rats.

OBJECTIVE: Available data suggest that estrogens and leptin play a role in the control of the pubertal process. In humans and some mammal species the increase of the activity of gonadotropic axis accompanies the decrease in the rate of growth at puberty. The effect of 17ß-estradiol and/or leptin administration on the somatotropic and gonadotropic axes was studied using prepubertal female rats as an animal model. MATERIAL AND METHODS: Prepubertal female rats received estradiol/saline, estradiol/leptin, oil/leptin or oil/saline (vehicles) respectively. The changes of growth rate, and serum 17ß-estradiol, leptin, GH, IGF-I and gonadotropins levels as well as LHRH and estrogen receptor (ER) concentrations in the medial basal hypothalamus (MBH) and the pituitary were determined. All hormones concentrations were measured by radioimmunoassay and ER by radioligand methods . RESULTS: In estradiol and/or leptin treated animals noticeable reduction of rate of growth was found. The decrease of growth in response to estradiol treatment accompanied the increase GH level and the decrease of IGF-I concentration in the circulation. Both hormones operating together activated reproductive axis, what was manifested by a significant increase of LHRH abundant in the hypothalamus as well as elevated LH and FSH levels in the circulation. In these rats a significant decrease of the estrogen receptor concentrations in the pituitary was observed. CONCLUSION: The role of estradiol and leptin in the control of growth and reproduction seems to overlap only partially. Estradiol plays a significant role in the activation of the reproductive axis, and leptin takes part as a permissive factor in pubertal process.

Decreased total serum adiponectin and its isoforms in women with acute ischemic stroke.

OBJECTIVE: An association between cerebral infarct risk factors and serum adiponectin levels (both total and separate isoforms) has previously been identified. The aim of this study was to assess circulating levels of all forms of adiponectin in the course of an ischemic stroke. MATERIAL AND METHODS: Adiponectin and its isoforms (HMW, MMW and LMW) were measured in serum samples taken from 38 women in the first 24 hours of cerebral infarct and 38 controls matched for gender, body mass index (BMI) and age. In addition, biochemical parameters (glucose, insulin, lipid profile) and clinical data (blood pressure, weight, and height) were evaluated. RESULTS: A significant reduction in serum levels of adiponectin and all examined fractions of this adipokine was observed in women suffering from acute ischemic stroke, compared with the matched controls. CONCLUSIONS: Differences in the serum adiponectin array between stroke subjects and controls were identified and further studies are required to investigate the clinical implications of this finding.

Valproate inhibits GnRH-induced gonadotropin release from anterior pituitary cells of male rat in vitro.

OBJECTIVE: Valproate (VPA) a potent antiepileptic drug has been claimed to induce reproductive disturbances in men. Long-term VPA treatment can affect sperm morphology and induce testicular atrophy in non-epileptic rats. It has been reported that VPA reduced testosterone secretion stimulated by hCG in isolated rat Leydig cells. These results suggest direct effect of VPA on testes in rats. However centrally mediated effects at hypothalamo-pituitary level can therefore not be excluded. This study focused on the dose and time-dependent effects of VPA on basal and GnRH-induced LH and FSH release from the primary anterior pituitary cells culture of male rats. MATERIAL AND METHODS: The dose-dependent effect of 10 nM-100 mM of VPA on basal LH release from anterior pituitary cells after 3h of incubation was examined. To determine the time-dependent effects on LH, FSH, TSH and PRL release short (3 h) and long-term (24 h) incubations in the presence of 10 nM, 100 nM and 1 µM of VPA were maintained.To assess whether VPA can affect GnRH-induced LH and FSH release, cells were incubated for 3 h with 10 nM, 100 nM and 1 µM of VPA in the presence of GnRH. The concentration of rLH, rFSH, rPRL and rTSH in incubation medium was determined by RIA method. RESULTS: VPA did not affect the basal LH, FSH, PRL and TSH release from the primary anterior pituitary cells culture of male rats. VPA in concentration 1µM significantly suppressed GnRH-induced LH secretion. However VPA at all tested doses diminished GnRH-induced FSH release. CONCLUSIONS: VPA may diminish gonadotropin release in vitro but this effect can only be achieved after GnRH-dependent specific receptor activation. Both gonadotropins differ in their pattern of response for increasing doses of VPA.

The influence of cocaine-amphetamine regulated transcript (CART) on pituitary hormones, corticosterone and leptin levels in starved rats.

OBJECTIVE: CART is involved in the control of food intake and hormonal secretion. We aimed to evaluate the effects of CART on hormonal profile in starved rats. METHODS: Study group included 100 male rats. Under conditions of food limitation CART (55-102) was given centrally (icv) or peripherally (iv). Non-starved animals underwent identical procedure. Vehicle (aCSF or saline)-injected rats served and as a controls. 60 minutes after CART or vehicle administration blood was collected to assess pituitary hormones (LH, FSH, PRL, GH, ACTH, TSH), corticosterone and leptin concentrations. RESULTS: Itracerebroventricular CART injection resulted in a significant increase in PRL, GH and corticosterone concentrations in non-starved rats compared with vehicle injected animals. However, in a group of starved animals only leptin levels were decreased in comparison with fasted controls. Peripheral CART administration caused a significant increase in PRL, GH and TSH levels in non-starved rats but no changes in investigated hormone levels were observed in starved animals when compared to saline injected controls. CONCLUSIONS: Our results indicate that CART is able to modulate hormonal profile in a non-starved rats. However, the modulatory effect depends on the CART administration method. Interestingly, CART administration, both icv and iv, does not have an impact on pituitary hormones and corticosterone levels in a course of food limitation.

Evaluation of orexin A activity on LH and FSH release from primary culture pituitary cells in immature and mature female rats.

OBJECTIVES: Orexin A (OxA) is a regulatory neuropeptide which is involved in the control of various autonomic and neuroendocrine functions. It regulates sleep-wake cycle, food intake and modulates the hypothalamic and pituitary hormones secretion. Orexin A acts through two types of receptors, which proved to exist in the pituitary. This may indicate the possibility of direct action of OxA on the adenohypophysis level. The aim of this study was to evaluate the direct effect of orexin A on gonadotropin (LH and FSH) release from cultured pituitary cells of immature female rats as well as mature female rats (ovariectomized and ovariectomized and estradiol treated rats). MATERIAL AND METHODS: The effect of 0.1 nM and 100 nM orexin A on LH and FSH release from anterior pituitary cells after 1 h of incubation was examined in immature female rats (IM) as well as mature female (ovariectomized - M/OVX; and ovariectomized and estradiol treated - M/OVX+E2) rats. The concentration of LH and FSH in medium was determined by RIA method. RESULTS: Orexin A at a dose of 0.1 nM and 100 nM significantly stimulated LH secretion in IM group. In M/OVX group release of LH was inhibited by OxA only in higher dose (100 nM). No effect of orexin A on FSH secretion was found. CONCLUSIONS: OxA may directly modulate LH secretion from cultured pituitary cells and it has the contradictory effect on LH release in immature and ovariectomized mature female rats.