Boguslawa Baranowska

The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, obesity, dyslipidemia and hypertension. Adiponectin, an adipocyte-specific protein with important roles in glucose and lipid homeostasis, possesses antidiabetic and insulin-sensitizing properties. Ghrelin, a protein ligand for the growth hormone secretagog receptor, has been shown to stimulate food intake and to influence energy balance, insulin signaling and glucose metabolism. We aimed to evaluate the relationships between metabolic alterations and adiponectin and ghrelin levels in lean PCOS women, compared with lean and obese women. The study was carried out on 20 non-obese PCOS women aged 20 – 48 years and age-matched groups of 45 healthy lean and 37 obese women. Hormonal and biochemical parameters, adiponectin and ghrelin concentrations and anthropometric data were determined. In PCOS subjects, we found increased homeostasis model assessment – insulin resistance index (HOMA-IR) with non-significant differences in adiponectin and ghrelin concentrations compared with healthy women, although the PCOS group showed a tendency to lower adiponectin levels. However, ghrelin levels in PCOS women were significantly higher than in obese women. Moreover, we observed a negative correlation between adiponectin and testosterone, cholesterol, triglycerides, glucose and diastolic blood pressure in PCOS. In conclusion, it can be suggested that higher values of HOMA-IR with lower adiponectin levels may indicate future development of metabolic syndrome or other metabolic disturbances in lean PCOS women.

Effects of cocaine-amphetamine regulated transcript (CART) on hormone release.

OBJECTIVE Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART is abundant in hypothalamus nuclei controlling anterior pituitary function. In the paraventricular nucleus CART mRNA is colocalized with vasopressin and corticotrophin-releasing factor containing neurons. The data may suggest that CART plays a role in hypothalamic regulation of neuroenocrine functions. MATERIAL AND METHODS Male Wistar-Kyoto rats were investigated. Experiment I: CART was administered intracerebroventricularly (i.c.v.) in a dose of 0.5 microg dissolved in 5 microl vehicle. At 60, 120 min after the infusion of CART or vehicle animals were decapitated and trunk blood was collected until hormonal estimations. Experiment II: CART in a dose of 10 microg was injected intravenously (i.v.). At 60, 120, 240 min the rats were decapitated and the trunk blood was collected. Serum rLH, rFSH, rPRL, rTSH, rGH and plasma leptin, NPY concentrations were measured by RIA methods. RESULTS CART administered centrally (i.c.v.) simulated significantly GH release after 60 min (p<0.05) and after 120 min (p<0.01). CART increased also PRL after 60 min (p<0.05). A marked increase of corticosterone level was observed at 60 and 120 min (p<0.01, p<0.01). We did not observe significant changes in LH, FSH and TSH. We found an increase of serum leptin concentrations at 60 min after CART administration (p<0.01). However, serum NPY levels did not change. After intravenous injection (i.v.) of CART an increase of GH was observed at 120, 240 min (p<0.01, p<0.01, respectively). A rise in serum PRL was found at 240 min (p<0.05). Corticosterone concentrations were enhanced at 60, 120, 240 min (p<0.01, p<0.01, p<0.01, respectively). We did not observe significant changes in LH, FSH and TSH. CONCLUSIONS CART may play a modulating role in the mechanism of pituitary hormone release.

Evaluation of neuroendocrine status in longevity.

It is well known that physiological changes in the neuroendocrine system may be related to the process of aging. To assess neuroendocrine status in aging humans we studied a group of 155 women including 78 extremely old women (centenarians) aged 100-115 years, 21 early elderly women aged 64-67 years, 21 postmenopausal women aged 50-60 years and 35 younger women aged 20-50 years. Plasma NPY, leptin, glucose, insulin and lipid profiles were evaluated, and serum concentrations of pituitary, adrenal and thyroid hormones were measured. Our data revealed several differences in the neuroendocrine and metabolic status of centenarians, compared with other age groups, including the lowest serum concentrations of leptin, insulin and T3, and the highest values for prolactin. We failed to find any significant differences in TSH and cortisol levels. On the other hand, LH and FSH levels were comparable with those in the elderly and postmenopausal groups, but they were significantly higher than in younger subjects. GH concentrations in centenarians were lower than in younger women. NPY values were highest in the elderly group and lowest in young subjects. We conclude that the neuroendocrine status in centenarians is markedly different from that found in early elderly or young women.

Vasoactive Intestinal Peptide Can Modulate Immune and Endocrine Responses during Lipopolysaccharide-Induced Acute Inflammation

Objectives: In many studies, it has been reported that vasoactive intestinal peptide (VIP) may play an important role in modulation of the immunological response. VIP can be produced by immunological cells, and also the receptors for this neuropeptide are present in many of these cells. The aim of our study was to estimate the effects of the administration of exogenous VIP on serum concentrations of proinflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and an anti-inflammatory cytokine (IL-10) during lipopolysaccharide (LPS)-induced acute inflammation. We also estimated the influence of VIP on pituitary [FSH, LH, TSH and prolactin (PRL)], thyroid (T3 and T4), adrenal (corticosterone) and gonadal (testosterone) hormones in response to LPS-induced acute inflammation. Methods: Male Wistar-Kyoto rats were divided into four groups, which received, respectively, placebo (0.9% NaCl), LPS, VIP and VIP with LPS. The TNF-α and IL-6 serum concentrations were measured after 2 h from the time of the administration of the agents, IL-10 was measured after 4 h, and the pituitary, thyroid, adrenal and gonadal hormone concentrations were measured after 2 and 4 h. Cytokine concentrations were estimated using ELISA tests, and hormone concentrations were measured using RIA tests. Results: In our experiments, LPS administration dramatically increased serum proinflammatory cytokine concentrations (TNF-α and IL-6) after 2 h and the anti-inflammatory cytokine (IL-10) after 4 h, as well as increasing the serum corticosterone concentration (after 2 and 4 h) and LH (after 2 h). LPS application decreased serum concentrations of T3 and TSH (both after 2 h), testosterone (after 2 and 4 h), FSH after 4 h and PRL after 4 h. VIP administration decreased the serum IL-10 concentration after 4 h and T3 concentration after 2 h and increased serum concentrations of FSH and corticosterone after 4 h. VIP administrated simultaneously with LPS decreased the LPS-induced increase in IL-6 and corticosterone concentrations (consecutively after 2 and 4 h). VIP also enhanced LPS-induced thyroid hormone (T3 and T4) suppression after 4 h and testosterone suppression after 4 h. Conclusion: We conclude that VIP can modulate not only immune responses but also hormonal responses during acute inflammation.

PACAP 38 as a modulator of immune and endocrine responses during LPS-induced acute inflammation in rats

The effect of PACAP 38 administration on neuroendocrine and immune parameters was examined in rats with LPS-induced peritonitis. Treatment with PACAP 38 alone did not influence the serum level of the cytokines and hormones examined, but significantly decreased immune cell activity. When administered together with LPS, PACAP 38 reversed its effect on immune and humoral parameters, causing a decrease in the serum concentrations of TNFalpha and corticosterone, and an increase in T4 and GH. The majority of PACAP 38 effects disappeared earlier than those previously observed for VIP. PACAP 38 appears to represent a short-lasting modulator of immune and endocrine responses during acute inflammation.

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

Alzheimers 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 Alzheimers 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.

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.

Identification of a Late Onset Alzheimer's Disease Candidate Risk Variant at 9q21.33 in Polish Patients

Late onset Alzheimers disease (LOAD) accounts for about 95% of all Alzheimers disease cases. While the APOE ε4 variant seems to have unparalleled influence on increased LOAD risk, it does not explain all of the heritability of LOAD. In this study, we present the application of a cost-effective, pooled DNA genome-wide association study (GWAS) to uncover genetic risk variants associated with LOAD in Polish women diagnosed with either mild cognitive impairment (MCI) or well-defined LOAD. A group of 141 patients (94 LOAD and 47 MCI), as well as 141 controls, were assayed using Affymetrix Genome-Wide Human SNP 6.0 arrays. Allele frequency distributions were compared using χ(2)-tests, and significantly associated SNPs at p < 0.0001 with a proxy SNP were selected. GWAS marker selection was conducted using PLINK, and selected SNPs were validated on DNA samples from the same cohort using KASPar Assays. In addition, to determine the genotype of APOE variants (rs429358, rs7412), a multiplex tetra-primer amplification refractory mutation system was applied. The GWAS revealed nine SNPs associated with MCI and/or LOAD. Of these, the association of seven SNPs was confirmed by genotyping of individual patients. Furthermore, the APOE ε4 appeared to be a risk variant for LOAD, while the APOE ε3 showed a protective effect. Multivariate analysis showed association between rs7856774 and LOAD, independently from the effect of APOE variation. Pooled DNA GWAS enabled the identification of a novel LOAD candidate risk variant, rs7856774 (9q21.33), tagging a possible genomic enhancer affecting proximal transcribed elements including DAPK1 gene.

Effect of orexin A on the release of GnRH-stimulated gonadotrophins from cultured pituitary cells of immature and mature female rats

Orexin A (OxA), also known as hypocretin 1, is a regulatory neuropeptide involved in the control of various autonomic and neuroendocrine functions. It appears to have a significant impact on the regulation of trophic hormones secretion by influencing the hypothalamus and the pituitary. Orexin A acts through two types of receptor found in the pituitary. This suggests the possibility of direct action of OxA at the adenohypophysis level. The aim of this study was to investigate the direct effect of OxA on GnRH (gonadotrophin-releasing hormone)-stimulated LH and FSH secretion from cultured pituitary cells of sexually immature and mature female rats. Anterior pituitary cells obtained from immature and mature female rats (ovariectomized, and ovariectomized and treated with estradiol) were incubated with 10(-10)M or 10(-7)M orexin A for 1 hour and 4h and the effect on GnRH-stimulated (10(-9)M or 10(-6)M) LH and FSH release was examined. The concentrations of secreted gonadotrophins in the culture media were determined by RIA methods. Orexin A significantly inhibited GnRH-stimulated FSH release from pituitary cells isolated from immature female rats, whereas in cells of mature ovariectomized animals, the effect of OxA was dependent on the stimulatory dose of GnRH. When the cells were stimulated with a low dose of GnRH, orexin A inhibited the secretion of gonadotrophins, but when a high dose of GnRH was used, orexin A increased mainly the release of LH. In cultured pituitary cells from ovariectomized, estrogenized mature rats, orexin A inhibited the secretion of LH if the cells were stimulated with a high dose of GnRH. In conclusion, the results of this study revealed that orexin A may modify the sensitivity of gonadotrophic cells to GnRH, and its effect depends on the maturity and estrogen status of the rats from which the cells are isolated.

Can PACAP-38 Modulate Immune and Endocrine Responses During Lipopolysaccharide (LPS)-Induced Acute Inflammation?

Abstract:  Pituitary adenylate cyclase‐activating polypeptide (PACAP) shows a potential anti‐inflammatory activity and interacts with the endocrine system. The aim of the present article was to evaluate the effects of PACAP38 on the endocrine and immune systems during acute inflammation. Rats used in the experiments, divided into four groups, were given intraperitoneal injection of, respectively 0.9% NaCl, LPS, PACAP38, and LPS+PACAP38. Hormone (pituitary, adrenal, and thyroid) and cytokine (TNF‐α, IL‐6, IL10) concentrations were measured 2 and 4 h after the injection. Treatment with LPS + PACAP, as compared to LPS, caused TNF‐α and corticosterone to decrease and T4 to increase after 2 h. These data suggest that PACAP modulates both the endocrine and immune responses in this model of septic shock.