Nicotinic acid attenuates amyloid ß1-42-induced mitochondrial dysfunction and inhibits the mitochondrial pathway of apoptosis in differentiated SH-SY5Y cells.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive memory loss and behavioral disorders. The excessive accumulation of amyloid ß (Aß) and the formation of neurofibrillary tangles (NFTs) damage synaptic connections and the death of neurons. However, the underlying mechanisms of pathogenesis of AD remain unclear. Growing evidence indicates that impaired mitochondrial function may play a crucial role in the development of AD. In the current study, we investigated whether nicotinic acid (NA) could protect against amyloid ß1-42-induced cytotoxicity in differentiated SH-SY5Y cells. Our results revealed the neuroprotective effects of NA on the differentiated SH-SY5Y cells treated with Aß1-42. In detail, the 1-h pre-incubation with NA increased cell viability and lowered LDH levels. NA pre-incubation abolished Aß1-42 treatment-associated alterations of mRNA levels of synaptic genes and enhanced the relative ß3 Tubulin fluorescence intensity. NA eliminated the Aß1-42-induced mitochondrial dysfunction by increasing the potential of mitochondrial membranes and maintaining a balance between the fusion and fission of mitochondria. Moreover, Aß1-42 decreased mRNA levels of anti-apoptotic bcl2 and increased mRNA levels of pro-apoptotic: bim, bak, cytochrome c, and caspase 9. At the same time, the NA pre-treatment reduced Aß1-42-dependent apoptotic death of differentiated SH-SY5Y cells. The above data suggest that NA presents a protective activity against Aß1-42-induced cytotoxicity in differentiated SH-SY5Y cells by inhibiting the mitochondrial pathway of apoptosis and restoring the proper function of mitochondria.

Obesity as a Risk Factor for Breast Cancer-The Role of miRNA.

Breast cancer (BC) is the most common cancer diagnosed among women in the world, with an ever-increasing incidence rate. Due to the dynamic increase in the occurrence of risk factors, including obesity and related metabolic disorders, the search for new regulatory mechanisms is necessary. This will help a complete understanding of the pathogenesis of breast cancer. The review presents the mechanisms of obesity as a factor that increases the risk of developing breast cancer and that even initiates the cancer process in the female population. The mechanisms presented in the paper relate to the inflammatory process resulting from current or progressive obesity leading to cell metabolism disorders and disturbed hormonal metabolism. All these processes are widely regulated by the action of microRNAs (miRNAs), which may constitute potential biomarkers influencing the pathogenesis of breast cancer and may be a promising target of anti-cancer therapies.

Exogenous orexin-A downregulates luteinizing hormone secretory activity in prepubertal female rats.

INTRODUCTION: Orexin-A is a neuropeptide synthesized in the lateral hypothalamus. Orexin-A immunoreactive fibres overlap distribution with GnRH neurons. In adult rats, orexin A is known to affect LH secretion via GnRH release modulation. Because data concerning the impact of orexin-A on the hypothalamo-pituitary axis activity are limited, we focused on the involvement of orexin-A and receptors of NPY in the modulation of LH release and LH subunit b (Lhb) mRNA expression in prepubertal female rats. MATERIAL AND METHODS: Forty immature female Wistar rats were divided into 4 groups and received 2 intracerebroventricular (icv) microinjections of: 1 - artificial cerebrospinal fluid (CSF) (controls); 2 - CSF followed by orexin A; 3 - selective NPY receptor antagonist (BIBP) followed by CSF; 4 - BIBP followed by orexin A. One hour after the last microinjection, all rats were decapitated. Trunk blood was collected, and serum was stored at -20°C for the LH RIA examination. The adenohypophysis was immediately excised, flash-frozen, and kept at -80°C for RNA extraction. Real-time PCR amplification was carried out, and relative Lhb gene expression was calculated. RESULTS: In comparison to the CSF-treated controls with a mean LH serum concentration of 0.40 ± 0.02 ng/mL, the mean LH serum level was diminished both after orexin-A (0.27 ± 0.01 ng/mL) and after BIBP (0.30 ± 0.02 ng/mL) icv microinjections. In the presence of BIBP, orexin-A more effectively inhibited LH release (0.20 ± 0.01 ng/mL) when compared to the BIBP-treated group. Orexin-A and BIBP exerted a consistent inhibitory effect on Lhb mRNA expression levels in the anterior pituitary gland. In comparison to the CSF-treated controls, orexin-A, and BIBP-treated females responded with, respectively, 35% and 40% reduction of Lhb mRNA expression. Orexin-A and BIBP co-administration evoked a further reduction of Lhb gene transcriptional activity. CONCLUSIONS: Orexin-A exerts a down-regulatory effect on LH synthesis and release in immature female rats. Considering that Y1R-oriented down-regulation of endogenous NPY activity did not reverse the suppressive effect of exogenous orexin-A, it might be suggested that NPY and orexin A systems can operate independently to affect gonadotropin activity in the anterior pituitary of the immature female rats.

All-trans-retinoic acid ameliorates atherosclerosis, promotes perivascular adipose tissue browning, and increases adiponectin production in Apo-E mice.

All-trans-retinoic acid (atRA), an active metabolite of vitamin A, exerts a potential role in the prevention of cardiovascular diseases. It has been shown that atRA ameliorates atherosclerosis while the exact mechanism underlying this protection remains unknown. This study investigated the influence of atRA on insulin resistance (IR), atherosclerosis, and the process of perivascular adipose tissue (PVAT) browning. Moreover, syntheses of adiponectin, adipokine with anti-atherogenic effects, and tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, were determined in PVAT. Apolipoprotein E-deficient mice (Apo-E) and control C57BL/6J wild-type mice were treated with atRA (5 mg/kg/day) or vehicle (corn oil) by plastic feeding tubes for 8 weeks. Long-term atRA treatment in Apo-E mice did not affect insulin resistance. AtRa administration ameliorated atherosclerosis, induced PVAT browning, and increased adiponectin production in PVAT in Apo-E mice. Furthermore, atRA increased nitric oxide (NO) level but did not affect adiponectin concentration in the aorta of Apo-E mice. These results indicate that atRA ameliorates atherosclerosis in Apo-E mice. We also observed the browning of PVAT. Besides, atRA increased the synthesis of adiponectin in PVAT and augmented NO level in the aorta in ApoE mice.

The Effects of Alpha-Linolenic Acid on the Secretory Activity of Astrocytes and ß Amyloid-Associated Neurodegeneration in Differentiated SH-SY5Y Cells: Alpha-Linolenic Acid Protects the SH-SY5Y cells against ß Amyloid Toxicity.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid ß- (Aß-) induced mitochondrial dysfunction may be a primary process triggering all the cascades of events that lead to AD. Therefore, identification of natural factors and endogenous mechanisms that protect neurons against Aß toxicity is needed. In the current study, we investigated whether alpha-linolenic acid (ALA), as a natural product, would increase insulin and IGF-I (insulin-like growth factor I) release from astrocytes. Moreover, we explored the protective effect of astrocytes-derived insulin/IGF-I on Aß-induced neurotoxicity, with special attention paid to their impact on mitochondrial function of differentiated SH-SY5Y cells. The results showed that ALA induced insulin and IGF-I secretion from astrocytes. Our findings demonstrated that astrocyte-derived insulin/insulin-like growth factor I protects differentiated SH-SY5Y cells against Aß 1-42-induced cell death. Moreover, pretreatment with conditioned medium (CM) and ALA-preactivated CM (ALA-CM) protected the SH-SY5Y cells against Aß 1-42-induced mitochondrial dysfunction by reducing the depolarization of the mitochondrial membrane, increasing mitochondrial biogenesis, restoring the balance between fusion and fission processes, and regulation of mitophagy and autophagy processes. Our study suggested that astrocyte-derived insulin/insulin-like growth factor I suppresses Aß 1-42-induced cytotoxicity in the SH-SY5Y cells by protecting against mitochondrial dysfunction. Moreover, the neuroprotective effects of CM were intensified by preactivation with ALA.

Peripheral levels of selected adipokines in patients with newly diagnosed multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. The exact aetiology is unknown. However, genetic and environmental factors are suggested to be involved in the pathogenesis of MS. Improper diet, resulting in obesity and metabolic syndrome, can contribute to this disease. Adipokines, secreted by adipose tissue, link the metabolism and immune system. MATERIAL AND METHODS: We aimed to assess plasma levels of selected adipokines in newly diagnosed, treatment-naïve individuals with multiple sclerosis. Our group comprised 58 individuals (31 MS patients and 27 controls, matched for age and BMI) without diabetes, hypertension, or dyslipidaemia. Circulating adiponectin and all adiponectin fractions, visfatin, and omentin concentrations were measured. Metabolic parameters were also assessed. RESULTS: In MS individuals we observed the following results: higher concentrations of visfatin, lower levels of omentin, and no differences in adiponectin array. There were also correlations between some adipokines and metabolic parameters. After adjustment to BMI, a significant decrease in total adiponectin, high-molecular weight (HMW) adiponectin and omentin, and an increase in medium-molecular-weight (MMW) adiponectin were observed in the group of MS patients when compared to those of the controls. CONCLUSIONS: Our results indicate that adiponectin with its fractions, visfatin, and omentin cannot be considered as causative factors in the early phase of multiple sclerosis. However, the potential role of adipokines in MS is possible because they might be involved in the pathogenesis of MS, regarded as an autoimmune disorder.

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.

Adipokine profile in patients with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is an eating disorder characterised with extremely low weight. Adipokines are adipose tissue-derived substances that show a wide spectrum of biological activities. We aimed to assess selected adipokine levels in women with AN before and after nutritional intervention. We also sought to examine whether BMI is the only confounding factor influencing adipokine assessment in AN. MATERIAL AND METHODS: Sixty-five women participated in the study: 20 individuals with AN before any treatment, 18 AN patients after nutritional intervention lasting for at least six months, and 27 women as controls. In all participants blood collection and anthropometric measurements were performed. ELISA was used for evaluation of leptin receptor, adiponectin and its isoforms, and resistin. Leptin was assessed with RIA, and visfatin was measured with EIA assay. RESULTS: Leptin and free leptin index (FLI) were lowest in treatment-naïve AN women. HMW-adiponectin and visfatin were enhanced in AN. Other adipokine levels showed no significant differences. When two subsets of anorexia nervosa were compared, only leptin, leptin receptor, and FLI were markedly different. When data were adjusted to BMI, leptin and FLI remained significantly different in the pre-treated AN subgroup when compared with the control group. CONCLUSIONS: Our results suggest that leptin is the most important adipokine in AN. It is also important that in our AN population leptin and FLI are the only factors that are influenced not only by the fat content.

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.

Effects of chymostatin, a chymase inhibitor, on blood pressure, plasma and tissue angiotensin II, renal haemodynamics and renal excretion in two models of hypertension in the rat.

NEW FINDINGS: What is the central question of this study? We examined, in hypertensive rats, whether the angiotensin-converting enzyme-independent enzymes generating angiotensin II in the tissues modulate blood pressure, peripheral circulation and renal function. What is the main finding and its importance? The results suggest that chymostatin-sensitive enzymes diminish vascular tone in renal and extrarenal vascular beds. Chymase or similar chymostatin-sensitive enzymes have a significant role in the synthesis of angiotensin II in different tissues but do not control blood pressure in the short term, similarly in salt-dependent or Goldblatt-type rat hypertension. In salt-dependent hypertension, chymase blockade protected renal outer medullary perfusion, probably by reducing the angiotensin II content in the kidney. Chymase is presumed to be a crucial enzyme of the non-angiotensin-converting enzyme pathway of angiotensin II (Ang II) generation in tissues, a process involved in vascular remodelling and development of hypertension. We examined the role of chymase in hypertension induced by exposure of uninephrectomized rats to high dietary salt intake (UNX HS) and in the Goldblatt renal artery stenosis (two-kidney, one-clip) model. In acute experiments with anaesthetized rats of either model, chymostatin at 2 mg kg(-1) h(-1) or 0.05% DMSO solvent was infused i.v. Mean arterial blood pressure, heart rate, iliac blood flow (a measure of hindlimb perfusion), total renal blood flow and intrarenal regional perfusion (laser-Doppler technique) were measured continuously, along with the glomerular filtration rate and renal excretion. In both models, chymase blockade distinctly decreased plasma and tissue Ang II without lowering mean blood pressure or consistently altering the other functional parameters measured. Unexpectedly, in Goldblatt hypertensive rats the blockade increased the renal and hindlimb vascular resistances by 51 and 33%, respectively (P < 0.05). In UNX HS hypertensive rats, chymase blockade abolished the solvent-induced decrease in outer medullary blood flow. We conclude that chymase or similar chymostatin-sensitive enzyme(s) has a significant role in the synthesis of Ang II in different tissues but does not participate in short-term control of blood pressure in salt-dependent or Goldblatt-type rat hypertension. In the Goldblatt model, chymase appeared to reduce the renal and hindlimb vascular resistances by an unknown mechanism. In salt-dependent hypertension, chymase blockade protected renal outer medullary perfusion, probably by reducing Ang II content in the kidney.

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.

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.

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.