scholarly journals Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate

2016 ◽  
Vol 101 (12) ◽  
pp. 4585-4593 ◽  
Author(s):  
Juilee Rege ◽  
Shigehiro Karashima ◽  
Antonio M. Lerario ◽  
Joshua M. Smith ◽  
Richard J. Auchus ◽  
...  
Keyword(s):  
Cytochrome B5 ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Zona Fasciculata ◽  
Adrenocortical Cells ◽  
Normal Children ◽  
Age Related ◽  
Age Dependent ◽  
Lyase Activity ◽  
Liquid Chromatography Tandem Mass

Context: Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation. Objective: This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A. Participants and Methods: Δ5-steroid sulfates were quantified by liquid chromatography–tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5–18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2–35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression. Results: Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production. Conclusion: Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.

scholarly journals The Age-Dependent Changes of the Human Adrenal Cortical Zones Are Not Congruent

2021 ◽  
Author(s):  
Yuta Tezuka ◽  
Nanako Atsumi ◽  
Amy R Blinder ◽  
Juilee Rege ◽  
Thomas J Giordano ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Adrenal Glands ◽  
Cytochrome B5 ◽  
Serum Cortisol ◽  
Zona Fasciculata ◽  
Serum Concentrations ◽  
Functional Changes ◽  
Sexual Dimorphisms ◽  
Age Related ◽  
Age Dependent

Abstract Background While previous studies indicate that the zonae reticularis (ZR) and glomerulosa (ZG) diminish with aging, little is known about age-related transformations of the zona fasciculata (ZF). Objectives To investigate the morphological and functional changes of the adrenal cortex across adulthood, with emphasis on (i) the understudied ZF and (ii) sexual dimorphisms. Methods We used immunohistochemistry to evaluate the expression of aldosterone synthase (CYP11B2), visinin-like protein 1 (VSNL1), 3β-hydroxysteroid dehydrogenase type II (HSD3B2), 11β-hydroxylase (CYP11B1), and cytochrome b5 type A (CYB5A) in adrenal glands from 60 adults (30 men), aged 18 to 86. Additionally, we employed mass spectrometry to quantify the morning serum concentrations of cortisol, 11-deoxycortisol (11dF), 17α-hydroxyprogesterone, 11-deoxycorticosterone, corticosterone, and androstenedione in 149 pairs of age- and body mass index–matched men and women, age 21 to 95 years. Results The total cortical area was positively correlated with age (r = 0.34, P = 0.008). Both the total (VSNL1-positive) and functional ZG (CYP11B2-positive) areas declined with aging in men (r = −0.57 and −0.67, P < 0.01), but not in women. The CYB5A-positive area declined with age in both sexes (r = −0.76, P < 0.0001). In contrast, the estimated ZF area correlated positively with age in men (r = 0.59, P = 0.0006) and women (r = 0.49, P = 0.007), while CYP11B1-positive area remained unchanged across ages. Serum cortisol, corticosterone, and 11-deoxycorticosterone levels were stable across ages, while 11dF levels increased slightly with age (r = 0.16, P = 0.007). Conclusion Unlike the ZG and ZR, the ZF and the total adrenal cortex areas enlarge with aging. An abrupt decline of the ZG occurs with age in men only, possibly contributing to sexual dimorphism in cardiovascular risk.

scholarly journals miR-155 Predicts Long-Term Mortality in Critically Ill Patients Younger than 65 Years

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Frank Tacke ◽  
Martina E. Spehlmann ◽  
Mihael Vucur ◽  
Fabian Benz ◽  
Mark Luedde ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Prognostic Biomarker ◽  
Serum Levels ◽  
Disease Etiology ◽  
Age Related ◽  
Age Dependent ◽  
Similar Accuracy

Introduction. Alterations in miR-155 serum levels have been described in inflammatory and infectious diseases. Moreover, a role for miR-155 in aging and age-related diseases was recently suggested. We therefore analyzed a potential age-dependent prognostic value of circulating miR-155 as a serum-based marker in critical illness. Methods. Concentrations of circulating miR-155 were determined in 218 critically ill patients and 76 healthy controls. Results. By using qPCR, we demonstrate that miR-155 serum levels are elevated in patients with critical illness when compared to controls. Notably, levels of circulating miR-155 were independent on the severity of disease, the disease etiology, or the presence of sepsis. In the total cohort, miR-155 was not an indicator for patient survival. Intriguingly, when patients were subdivided according to their age upon admission to the ICU into those younger than 65 years, lower levels of miR-155 turned out as a strong marker, indicating patient mortality with a similar accuracy than other markers frequently used to evaluate critically ill patients on a medical ICU. Conclusion. In summary, the data provided within this study suggest an age-specific role of miR-155 as a prognostic biomarker in patients younger than 65 years. Our study is the first to describe an age-dependent miRNA-based prognostic biomarker in human diseases.

scholarly journals The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis

2010 ◽  
Vol 205 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Sebastio Perrini ◽  
Luigi Laviola ◽  
Marcos C Carreira ◽  
Angelo Cignarelli ◽  
Annalisa Natalicchio ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Signs And Symptoms ◽  
Well Being ◽  
Serum Levels ◽  
Normal Range ◽  
Gh Secretion ◽  
Skeletal Muscle Wasting ◽  
Age Related ◽  
Age Dependent

The widespread increase in life expectancy is accompanied by an increased prevalence of features of physical frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced exercise capacity, and diminished sense of well-being. The pathogenesis of age-associated sarcopenia and osteopenia is multifactorial, and hormonal decline may be a contributing factor. Aging is associated with a progressive decrease in GH secretion, and more than 30% of elderly people have circulating IGF1 levels below the normal range found in the young. GH acts directly on target tissues, including skeletal muscle and bone among many others, but many effects are mediated indirectly by circulating (liver-derived) or locally produced IGF1. Aging is also associated with reduced insulin sensitivity which, in turn, may contribute to the impairment of IGF1 action. Recent experimental evidence suggests that besides the age-dependent decline in GH and IGF1 serum levels, the dysregulation of GH and IGF1 actions due to impairment of the post-receptor signaling machinery may contribute to the loss of muscle mass and osteopenia. This article will focus on the molecular mechanisms of impaired GH and IGF1 signaling and action in aging, and their role in the pathogenesis of sarcopenia and osteoporosis.

scholarly journals Sex- and Age-Related Changes in Epitestosterone in Relation to Pregnenolone Sulfate and Testosterone in Normal Subjects

2002 ◽  
Vol 87 (5) ◽  
pp. 2225-2231 ◽  
Author(s):  
Helena Havlíková ◽  
Martin Hill ◽  
Richard Hampl ◽  
Luboš Stárka
Keyword(s):  
Sharp Decrease ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Pregnenolone Sulfate ◽  
Men And Women ◽  
Age Related ◽  
Age Dependent ◽  
Prepubertal Boys ◽  
Age Related Changes

Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor pregnenolone sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20 yr of age, followed by a continuous decline up to menopause and by a further increase in the postmenopause. In men, maximum epitestosterone levels were detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone sulfate levels in women reached their maximum at about age 32 yr and then declined continuously, and in males the maximum was reached about 5 yr earlier and then remained nearly constant. Epitestosterone correlated with pregnenolone sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T ratio around puberty occurred. In conclusion, concentrations of epitestosterone and pregnenolone sulfate are age dependent and, at least in prepubertal boys and girls, epitestosterone reaches or even exceeds the concentrations of T, thus supporting its role as an endogenous antiandrogen. The dissimilarities in the course of epitestosterone levels through the lifespan of men and women and its relation to pregnenolone sulfate concentrations raise the question of the contribution of the adrenals and gonads to the production of both steroids and even to the uniformity of the mechanism of epitestosterone formation.

scholarly journals Circulating miRNA expression in asthmatics is age-related and associated with clinical asthma parameters, respiratory function and systemic inflammation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aleksandra Wardzyńska ◽  
Małgorzata Pawełczyk ◽  
Joanna Rywaniak ◽  
Joanna Makowska ◽  
Joanna Jamroz-Brzeska ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Mirna Expression ◽  
Serum Levels ◽  
Control Group ◽  
Serum Mirna ◽  
Age Related ◽  
Age Dependent ◽  
Elderly Asthmatics ◽  
Clinical Asthma ◽  
Lower Expression

Abstract Background The course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA. Methods Control and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry. Results No difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs. Conclusion Serum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.

scholarly journals The Primate Adrenal Zona Reticularis is Defined by Expression of Cytochrome b5, 17α-hydroxylase/17,20-lyase Cytochrome P450 (P450c17) and NADPH-Cytochrome P450 Reductase (reductase) but not 3β-Hydroxysteroid Dehydrogenase/Δ5-4 Isomerase (3β-HSD)

1999 ◽  
Vol 84 (9) ◽  
pp. 3382-3385 ◽  
Author(s):  
Samantha Mapes ◽  
C. Jo Corbin ◽  
Alice Tarantal ◽  
Alan Conley
Keyword(s):  
Cytochrome P450 ◽  
Functional Role ◽  
Cytochrome B5 ◽  
Zona Fasciculata ◽  
Cytochrome P450 Reductase ◽  
Efficient Synthesis ◽  
Zona Reticularis ◽  
Regional Control ◽  
Biochemical Studies ◽  
Lyase Activity

Biochemical studies suggest that 17,20-lyase activity, and thus efficient synthesis of androgens by human P450c17, requires both reductase and the accessory protein cytochrome b5. Since the human and primate zona reticularis (ZR) secrete androgens, the expression of these proteins, and of 3β-HSD, was investigated by immunocytochemistry in the adrenal cortex of the mature rhesus macaque. Cytochrome b5 expression was restricted to the cells of the ZR which appeared deficient in 3β-HSD. However, both P450c17 and reductase were evident throughout the zona fasciculata. These data provide essential evidence in support of a functional role for cytochrome b5 in the regional control of 17α-hydroxylase and 17,20-lyase activities of P450c17 and thereby adrenal C19 steroid secretion by the primate adrenal gland.

scholarly journals Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence

2009 ◽  
Vol 203 (2) ◽  
pp. 241-252 ◽  
Author(s):  
Xiao-Gang Hui ◽  
Jun-ichi Akahira ◽  
Takashi Suzuki ◽  
Masaki Nio ◽  
Yasuhiro Nakamura ◽  
...  
Keyword(s):  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Adrenal Androgen ◽  
Zona Reticularis ◽  
Age Related ◽  
Morphometric Analyses ◽  
Proliferation And Apoptosis ◽  
Age Dependent ◽  
Autopsy Specimens ◽  
Immunohistochemical Studies

Age-related morphologic development of human adrenal zona reticularis (ZR) has not been well examined. Therefore, in this study, 44 human young adrenal autopsy specimens retrieved from large archival files (n=252) were examined for immunohistochemical and morphometric analyses. Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age. The number of BCL2-positive cells increased in ZR and decreased in ZF during development. Adrenal androgen synthesizing type 5 17β-hydroxysteroid dehydrogenase (HSD17B5 or AKR1C3 as listed in the Hugo Database) was almost confined to ZR of human adrenals throughout development. HSD17B5 immunoreactivity in ZR became discernible and increased from around 9 years of age. Results of our present study support the theory of age-dependent adrenocortical cell migration and also indicated that ZR development is not only associated with adrenarche, but may play important roles in an initiation of puberty.

scholarly journals In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Whole Blood ◽  
Serum Levels ◽  
Reversed Phase ◽  
Weekly Treatment ◽  
Low Dose Aspirin ◽  
Liquid Chromatography Tandem Mass ◽  
Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

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