Corticosteroid-Binding Globulin is expressed in the adrenal gland and its absence impairs corticosterone synthesis and secretion in a sex-dependent manner

Corticosteroid-binding globulin (CBG) is synthesized by the liver and secreted into the bloodstream where binds to glucocorticoids. Thus CBG has the role of glucocorticoid transport and free hormone control. In addition, CBG has been detected in some extrahepatic tissues without a known role. CBG-deficient mice show decreased total corticosterone levels with missing of classical sexual dimorphism, increased free corticosterone, higher adrenal gland size and altered HPA axis response to stress. Our aim was to ascertain whether CBG deficiency could affect the endocrine synthetic activity of adrenal gland and if the adrenal gland produces CBG. We determined the expression in adrenal gland of proteins involved in the cholesterol uptake and its transport to mitochondria and the main enzymes involved in the corticosterone, aldosterone and catecholamine synthesis. The results showed that CBG is synthesized in the adrenal gland. CBG-deficiency reduced the expression of ACTH receptor, SRB1 and the main genes involved in the adrenal hormones synthesis, stronger in females resulting in the loss of sexual dimorphism in corticosteroid adrenal synthesis, despite corticosterone content in adrenal glands from CBG-deficient females was similar to wildtype ones. In conclusion, these results point to an unexplored and relevant role of CBG in the adrenal gland functionality related to corticosterone production and release

Introducció de l'Aprenentatge Servei al grau de Ciències Ambientals

Aquesta comunicació presenta el projecte Aplicació de l'Aprenentatge Servei a la Facultat de Biologia: implementació d'iniciatives que promoguin el desenvolupament sostenible del nostre entorn, d'aplicació a l'assignatura de Desenvolupament Sostenible del Grau de Ciències Ambientals (UB). És un projecte d'APS on els alumnes desenvolupen una idea fins a convertir-la en un projecte que millori la sostenibilitat social i mediambiental de l'entorn, col·laborant amb entitats socials d'aquest àmbit

New roles for corticosteroid binding globulin and opposite expression profiles in lung and liver.

Corticosteroid-binding globulin (CBG) is the specific plasma transport glycoprotein for glu- cocorticoids. Circulating CBG is mainly synthesized in liver but, its synthesis has been located also in other organs as placenta, kidney and adipose tissue with unknown role. Using an experimental model of acute pancreatitis in cbg -/- mice we investigated whether changes in CBG affect the progression of the disease as well as the metabolism of gluco- corticoids in the lung. Lack of CBG does not modify the progression of inflammation associ- ated to pancreatitis but resulted in the loss of gender differences in corticosterone serum levels. In the lung, CBG expression and protein level were detected, and it is noteworthy that these showed a sexual dimorphism opposite to the liver, i.e. with higher levels in males. Reduced expression of 11 β -HSD2, the enzyme involved in the deactivation of corticoste- rone, was also observed. Our results indicate that, in addition to glucocorticoids transporter, CBG is involved in the gender differences observed in corticosteroids circulating levels and plays a role in the local regulation of corticosteroids availability in organs like lung

Effect of cafeteria diet feeding on soleus intramyocellular lipid of Wistar rats

Background: The presence of lipid besides muscle fibres facilitates the energy supply for exercise, but it is also indicative of insulin resistance in the untrained. Muscle lipid is associated with increased dietary energy: hyperlipidic diets induce an increase in intramyocellular lipid deposition in skeletal muscle. Methods: In the present study we analyzed the changes in soleus (a red-fibre muscle) intracellular muscle content under a hyperlipidic (cafeteria) diet in Wistar rats. We also analyzed in parallel the mitochondrial content a relative index of energy output capability. Results: Cafeteria diet-fed rats contained more lipid and mitochondria per unit of muscle section area than controls. Conclusions: The correlation found in the increases of muscle lipid and mitochondria hit at this increase as an adaptation of muscle to oxidize excess energy substrates under conditions of excess energy availability, probably contributing to adaptive thermogenesis

Oleoyl-estrone is a precursor of an estrone-derived ponderostat signal

Oleoyl-estrone (OE) is a powerful anti-obesity compound that decreases food intake, decreases insulin resistance and circulating cholesterol. OE stimulates a severe loss of body fat by decreasing adipose tissue lipid synthesis and maintaining lipolysis. Therefore, the body economy loses lipid energy because energy expenditure is maintained. This study analyses the discrepancy between OE effects and the distribution of labelled OE in plasma. Estrone radioimmunoassay of organic solvent plasma extracts of rats treated with OE showed the massive presence of acyl-estrone, but. saponification did not release estrone, but containing similar unknown compound. Analysis of label distribution in plasma after oral gavages of 3H-OE showed the presence of a more hydrophilic compound than OE or any estrogen as well as 3H2O, formed from 3H-OE in the acidic stomach medium. OE was not attached toa specific transporter in plasma. Through serum HPLC analysis we found W, a labelled derivative more hydrophilic than OE or estrone. The results were confirmed using 14C-OE. HPLC-MS/MS studies showed that plasma OE levels were one order of magnitude lower than those of W. When liver cell cytosols from rats laden with 3H-OE were incubated with nuclei from untreated rats, the OE-derived label (i.e., W's) was found attached to nuclear DNA. Neither estradiol nor estrone interfered with its binding. W is a fairly hydrophilic compound of low molecular weight containing the estrone nucleus, but it is not an ester because saponification or esterases do not yield estrone as OE does. It is concluded that OE acts through its conversion to W, its active form; which binds to a nuclear receptor different from that of estrogen. The estimated W serum levels are proportional to the pharmacological OE effects in vivo. We postulate W as a new type of hormone that exerts the full range of in vivo effects thus far attributed to OE. The full identification of W is anticipated to open the way for the development of new OE-like anti-obesity drugs

Purging behavior modulates the relationships of hormonal and behavioral parameters in women with eating disorders

Background/aims: There is ample consensus that there is a neurophysiological basis for the eating disorders (ED). Traits of personality translate into behavioural traits, purging being a well defined transversal example. Direct implication of steroid hormones on ED has been seldom studied, despite their effects on behaviour. Methods: After psychological interview analysis 57 ED female patients (31 purgative and 26 non-purgative), and 17 female controls were studied. Metabolic parameters and analysis of androgen, estrogen and glucocorticoid hormones were determined in parallel to the psychopathological profile (EDI-2 and SCL-90-R) and anthropometric measurements. Results: Psychometric tests showed clear differences between ED and controls, but there were few hormonal-metabolic significant differences. In purgative ED there were repeated (significant) positive correlations with CBG, and negative with SHBG, versus eating and general psychopathology. In non-purging, there were positive correlations for deoxycortisol, free fatty acids, albumin and negative for aspartate aminotransferase and psychopathological traits. Conclusion: The data hint at CBG/corticosteroids and sexual hormones/SHBG to be involved in purging behaviour and its psychopathology and severity scores. Correlations of selected psychometric data and the CBG/SHBG levels in purging may eventually result in clinical markers. This approach may provide additional clues for understanding the pathogenesis of the ED

Corticosteroid-binding-globulin (CBG)-deficient mice show high pY216-GSK3β and phosphorylated-Tau levels in the hippocampus

Corticosteroid-binding globulin (CBG) is the specific carrier of circulating glucocorticoids, but evidence suggests that it also plays an active role in modulating tissue glucocorticoid activity. CBG polymorphisms affecting its expression or affinity for glucocorticoids are associated with chronic pain, chronic fatigue, headaches, depression, hypotension, and obesity with an altered hypothalamic pituitary adrenal axis. CBG has been localized in hippocampus of humans and rodents, a brain area where glucocorticoids have an important regulatory role. However, the specific CBG function in the hippocampus is yet to be established. The aim of this study was to investigate the effect of the absence of CBG on hippocampal glucocorticoid levels and determine whether pathways regulated by glucocorticoids would be altered. We used cbg-/- mice, which display low total-corticosterone and high free-corticosterone blood levels at the nadir of corticosterone secretion (morning) and at rest to evaluate the hippocampus for total- and free-corticosterone levels; 11β-hydroxysteroid dehydrogenase expression and activity; the expression of key proteins involved in glucocorticoid activity and insulin signaling; microtubule-associated protein tau phosphorylation, and neuronal and synaptic function markers. Our results revealed that at the nadir of corticosterone secretion in the resting state the cbg-/- mouse hippocampus exhibited slightly elevated levels of free-corticosterone, diminished FK506 binding protein 5 expression, increased corticosterone downstream effectors and altered MAPK and PI3K pathway with increased pY216-GSK3β and phosphorylated tau. Taken together, these results indicate that CBG deficiency triggers metabolic imbalance which could lead to damage and long-term neurological pathologies

Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review.

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-β), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1β), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-β, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected

Impulso del compromiso de los estudiantes universitarios mediante procesos de codiseño

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/164579[spa] El impulso del compromiso de los estudiantes universitarios mediante procesos de codiseño se basa en establecer una relación de partenariado entre estudiantes y profesorado en un proceso de colaboración recíproca. El objetivo general de la investigación presentada es codiseñar espacios de aprendizaje universitarios mediante la participación directa de los estudiantes. La metodología usada es la investigación basada en el diseño. Los sujetos de estudio son docentes y estudiantes universitarios de Educación Social, Pedagogía, Trabajo Social, Enfermería y Biología en asignaturas de tipología diferente (obligatorias, optativas, prácticum y créditos de libre reconocimiento) y en distintos contextos de participación y toma de decisión (contenidos, evaluación y metodologías pedagógicas). Los resultados obtenidos permiten realizar una descripción teórico-práctica de estrategias de codiseño de escenarios de aprendizaje y participación.[eng] University students’ engagement through co-design processes is based on establishing a mutual collaboration partnership between students and professors. The purpose of this paper is to inquire, conceptualize and co-design university learning spaces through students’ direct participation. The used methodology is design-based research. The subjects of this study are university professors and students of Social Education, Pedagogy, Social Work, Nursery, and Biology, in different subject areas —compulsory lectures, electives, practicum and open credit— and in different participation and decision-making contexts —content, evaluation, and pedagogic methodologies—. A theoretical and practical description of co-design strategies of learning and participation scenarios are allowed by the obtained results

Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity.

Objective: Sex hormone-binding globulin (SHBG) binds and transports testosterone and estradiol in plasma. The possibility that SHBG is a mixture of transporting proteins has been postulated. We analyzed in parallel the effects of obesity status on the levels and binding capacity of circulating SHBG and their relationship with testosterone and estradiol.Design: Anthropometric measures and plasma were obtained from apparently healthy young (i.e. 35 +/- 7 years) premenopausal women (n = 32) and men (n = 30), with normal weight and obesity (BMI > 30 kg/m(2)).Methods: SHBG protein (Western blot), as well as the plasma levels of testosterone, estradiol, cortisol and insulin (ELISA) were measured. Specific binding of estradiol and testosterone to plasma SHBG was analyzed using tritiumlabeled hormones.Results: Significant differences in SHBG were observed within the obesity status and gender, with discordant patterns of change in testosterone and estradiol. In men, testosterone occupied most of the binding sites. Estrogen binding was much lower in all subjects. Lower SHBG of morbidly obese (BMI > 40 kg/m(2)) subjects affected testosterone but not estradiol. The ratio of binding sites to SHBG protein levels was constant for testosterone, but not for estradiol. The influence of gender was maximal in morbid obesity, with men showing the highest binding/SHBG ratios.Conclusions: The results reported here are compatible with SHBG being a mixture of at least two functionally different hormone-binding globulins, being affected by obesity and gender and showing different structure, affinities for testosterone and estradiol and also different immunoreactivity