scholarly journals Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment?

2021 ◽  
Vol 55 (3) ◽  
pp. 174-181
Author(s):  
Sojit Tomo ◽  
Mithu Banerjee ◽  
Praveen Sharma ◽  
Mahendra Garg
Keyword(s):  
Rheumatoid Arthritis ◽  
Hpa Axis ◽  
Acute Stress ◽  
Immunological Response ◽  
Dehydroepiandrosterone Sulfate ◽  
Inhibitory Effect ◽  
Limited Evidence ◽  
Inflammatory Conditions ◽  
Acute Stress Response

Abstract The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.

scholarly journals The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus

2019 ◽  
Author(s):  
Alexander S. Häusl ◽  
Jakob Hartmann ◽  
Max L. Pöhlmann ◽  
Lea M. Brix ◽  
Juan-Pablo Lopez ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Acute Stress ◽  
Negative Regulator ◽  
Immune Disorders ◽  
Fk506 Binding Protein ◽  
Main Driver ◽  
Acute Stress Response

Disturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), a main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. Using deletion, overexpression, and rescue of Fkbp5 exclusively in the PVN, we establish the fundamental importance of Fkbp5 in the HPA axis stress response. Furthermore, we show that Fkbp5 manipulation alters GR activation and elucidate the cellular complexity in the PVN, in which Fkbp5 operates.

scholarly journals The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus of male mice

2021 ◽  
Author(s):  
Alexander S. Häusl ◽  
Lea M. Brix ◽  
Jakob Hartmann ◽  
Max L. Pöhlmann ◽  
Juan-Pablo Lopez ◽  
...  
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Paraventricular Nucleus ◽  
Acute Stress ◽  
Negative Regulator ◽  
Neuron Activity ◽  
Cell Type ◽  
Specific Expression ◽  
Acute Stress Response ◽  
Cell Type Specific

AbstractDisturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic, and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. We here demonstrate that the deletion of Fkbp5 in Sim1+ neurons dampens the acute stress response and increases GR sensitivity. In contrast, Fkbp5 overexpression in the PVN results in a chronic HPA axis over-activation, and a PVN-specific rescue of Fkbp5 expression in full Fkbp5 KO mice normalizes the HPA axis phenotype. Single-cell RNA sequencing revealed the cell-type-specific expression pattern of Fkbp5 in the PVN and showed that Fkbp5 expression is specifically upregulated in Crh+ neurons after stress. Finally, Crh-specific Fkbp5 overexpression alters Crh neuron activity, but only partially recapitulates the PVN-specific Fkbp5 overexpression phenotype. Together, the data establish the central and cell-type-specific importance of Fkbp5 in the PVN in shaping HPA axis regulation and the acute stress response.

Acute Stress Induced Behavioral Deficits In Rats: Relationship With Oxidative Stress, Leptin And HPA Axis

2019 ◽  
Vol 41 (5) ◽  
pp. 859-859
Author(s):  
Erum Shireen Erum Shireen ◽  
Wafa Binte Ali Wafa Binte Ali ◽  
Maria Masroor Maria Masroor ◽  
Saeeda Bano Saeeda Bano ◽  
Samina Iqbal Samina Iqbal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Hpa Axis ◽  
Acute Stress ◽  
Antioxidant Properties ◽  
Oxidative Enzymes ◽  
Behavioral Deficits ◽  
Glucose Estimation ◽  
Dark Transition

Acute exposure to stress is connected to many disorders that promote the toxicity of oxygen radical generators leading to increase in the levels of enzymes and also the activation of the HPA axis. The present study uses a preclinical approach to elucidate some prospective stress-induced behavioral and biochemical effects. The aim of current study was to investigate the relationship between stress and behavioral changes after exposing animals to 2h immobilization stress. We also evaluated the concentration of corticosterone, glucose and endogenous leptin levels in unstressed and stressed animals to explore the possible role of HPA axis in the modulation of stressed induced behavioral deficits. Rats were divided into stressed and unstressed groups. Behavioral activities were monitored in open field activity and light dark transition box after the termination of 2h immobilization period. Animals were then decapitated and plasma samples were collected for catalase, SOD, corticosterone, and glucose estimation. Results showed that exposure to acute stress produced a significant decrease in the activity of rats in the novel environment (open field) and light dark transition box. On the other hand, concomitant elevated level of peripheral markers of oxidative stress such as oxidative enzymes, corticosterone and endogenous leptin were also observed. Therefore, current study seems to suggest an important role of compounds having antioxidant properties for the treatment of stress and related disorders.

scholarly journals The Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage

2021 ◽  
Vol 3 ◽  
Author(s):  
Joanne Muter ◽  
Chow-Seng Kong ◽  
Jan J. Brosens
Keyword(s):  
Stromal Cells ◽  
Acute Stress ◽  
Embryo Implantation ◽  
Recurrence Risk ◽  
Tissue Remodelling ◽  
Endometrial Stromal Cells ◽  
Decidual Cells ◽  
Unk Cells ◽  
Acute Stress Response

In each menstrual cycle, the endometrium becomes receptive to embryo implantation while preparing for tissue breakdown and repair. Both pregnancy and menstruation are dependent on spontaneous decidualization of endometrial stromal cells, a progesterone-dependent process that follows rapid, oestrogen-dependent proliferation. During the implantation window, stromal cells mount an acute stress response, which leads to the emergence of functionally distinct decidual subsets, reflecting the level of replication stress incurred during the preceding proliferative phase. Progesterone-dependent, anti-inflammatory decidual cells (DeC) form a robust matrix that accommodates the conceptus whereas pro-inflammatory, progesterone-resistant stressed and senescent decidual cells (senDeC) control tissue remodelling and breakdown. To execute these functions, each decidual subset engages innate immune cells: DeC partner with uterine natural killer (uNK) cells to eliminate senDeC, while senDeC co-opt neutrophils and macrophages to assist with tissue breakdown and repair. Thus, successful transformation of cycling endometrium into the decidua of pregnancy not only requires continuous progesterone signalling but dominance of DeC over senDeC, aided by recruitment and differentiation of circulating NK cells and bone marrow-derived decidual progenitors. We discuss how the frequency of cycles resulting in imbalanced decidual subpopulations may determine the recurrence risk of miscarriage and highlight emerging therapeutic strategies.

Influence of nandrolondecanoate on the pituitary-gonadal axis in males

1982 ◽  
Vol 101 (1) ◽  
pp. 108-112 ◽  
Author(s):  
J. W. J. Bijlsma ◽  
S. A. Duursma ◽  
J. H. H. Thijssen ◽  
O. Huber
Keyword(s):  
Rheumatoid Arthritis ◽  
Pilot Study ◽  
Beneficial Effect ◽  
Sex Steroids ◽  
Anabolic Steroids ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Testosterone Secretion ◽  
Lh Secretion

Abstract. Different anabolic steroids can exercise different effects on the pituitary-gonadal axis in males. During a pilot study regarding the possible beneficial effect of the anabolic steroid nandrolondecanoate (ND) on bone metabolism in patients with rheumatoid arthritis additional endocrinological parameters were studied. A significant decrease was found in the serum levels of testosterone, androstenedione and FSH and the ratio of testosterone/oestradiol. There was a significant increase in the serum levels of oestrone. The levels of oestradiol, SHBG, LH and cortisol remained unchanged. An inhibitory effect of ND on testicular testosterone secretion is assumed. The decrease in androstenedione levels is explained by the diminished testosterone secretion. The rise in oestrone levels is explained by peripheral aromatizing of ND to oestrogens. The presented findings are in accordance with the hypothesis that sex steroids can act directly on the pituitary resulting in selective FSH and LH secretion. The possible role of the ratio testosterone/oestradiol in controlling gonadotrophin output is discussed.

scholarly journals Possible Influence of Resistance to Malaria in Clinical Presentation of Rheumatoid Arthritis: Biological Significance of Natural Selection

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Fabio Bonilla-Abadía ◽  
Gabriel J. Tobón ◽  
Carlos A. Cañas
Keyword(s):  
Rheumatoid Arthritis ◽  
Natural Selection ◽  
Chemokine Receptors ◽  
Biological Significance ◽  
Immunological Response ◽  
Immune Reactivity ◽  
Loss Of Function ◽  
Special Group ◽  
Increased Risk

Rheumatoid arthritis (RA) is a common autoimmune disease that affects all ethnic groups. Genetic factors, mainly HLA alleles, are highly associated with increased risk to develop RA. However, there are few available data about the role of these genetic polymorphisms in the prevalence or severity of RA in the Afrodescendant population, who have evolutionarily and by natural selection developed mutations that allowed them to acquire resistance to infectious diseases like malaria. Some of the mechanisms, by which this resistance was developed as a product of natural selection, are involved in different forms of immunological response, many of them of a well-known importance in the pathophysiology of RA. This paper focuses on presenting the known mechanisms of resistance to malaria and their possible contribution to the pathophysiology of RA, including “loss-of-function” mutations, lack of expression of chemokine receptors, decrease of immune complexes clearance by asplenia, or increase of immune reactivity mediated by B cells, among other mechanisms in this special group of patients.

scholarly journals Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

2009 ◽  
Vol 106 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Jonathan E. Campbell ◽  
Nasimeh Rakhshani ◽  
Sergiu Fediuc ◽  
Silvio Bruni ◽  
Michael C. Riddell
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
Restraint Stress ◽  
Acute Stress ◽  
Wheel Running ◽  
Male Rats ◽  
Voluntary Wheel Running ◽  
Acute Stress Response ◽  
Voluntary Wheel

Although exercise is a common and potent activator of the hypothalamic-pituitary adrenal (HPA) axis, the effects of exercise on the acute stress response are not well understood. Here, we investigated the effects of short- (2 wk) and long-term (8 wk) voluntary wheel running on adrenal sensitivity to ACTH stimulation and the acute stress response to restraint in male rats. Diurnal glucocorticoid patterns were measured on days 7 (all groups) and 35 (8-wk groups). Rats were subjected to 20 min of restraint stress on either week 1 or on week 7 of treatment to assess HPA activation. One week later, exogenous ACTH (75 ng/kg) was administered to assess adrenal sensitivity to ACTH. Following this, adrenals were collected and analyzed for key proteins involved in corticosterone (CORT) synthesis. By the end of week 1, exercising (E) animals had twofold higher peak diurnal CORT levels compared with sedentary (S) animals ( P < 0.01). CORT values were not different between groups at week 8. In response to restraint stress at week 2, CORT values in E were approximately threefold greater than in S ( P < 0.05). No difference was found between E and S rats in the response to, or recovery from, restraint at week 8. During the ACTH challenge at week 2, E demonstrated a ∼2.5-fold increase in adrenal sensitivity compared with S, while no difference was found between E and S at week 8. The expression of steroidogenic acute regulatory protein was found to be ∼50% higher in the adrenals in E compared with S at week 2 ( P < 0.05), but no difference existed between groups at week 8. These results show that volitional wheel running initially causes hyperactivation of the HPA axis, due to enhanced adrenal sensitivity to ACTH, but that these alterations in HPA activity are completely restored by 8 wk of training.

scholarly journals The Role of Alcohol Biomarkers in Detecting a Physician's COVID-19-Related Acute Stress Response

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Alexis G. Polles ◽  
William S. Jacobs ◽  
Chad Brazle ◽  
Lisa J. Merlo
Keyword(s):  
Stress Response ◽  
Acute Stress ◽  
Acute Stress Response

scholarly journals Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR

2021 ◽  
Vol 11 (1) ◽  
pp. 120
Author(s):  
Gabriela Athziri Sánchez-Zuno ◽  
Richard Bucala ◽  
Jorge Hernández-Bello ◽  
Ilce Valeria Román-Fernández ◽  
Mariel García-Chagollán ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Expression Patterns ◽  
Membrane Receptors ◽  
High Disease Activity ◽  
Clinical Activity ◽  
Inflammatory Conditions ◽  
Type Receptor ◽  
Elisa Data

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. Methodology: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. Results: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). Conclusions: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.

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