Reduction In Cortisol Secretion Research Articles

Sublethal Hyperthermia Transiently Disrupts Cortisol Steroidogenesis in Adrenocortical Cells.

Primary aldosteronism is the most common cause of secondary hypertension. The first-line treatment adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone-producing adenomas, while preserving adjacent normal adrenal cortex. To determine the extent of damage to adrenal cells upon exposure to hyperthermia, the steroidogenic adrenocortical cell lines H295R and HAC15 were treated with hyperthermia at temperatures between 37 and 50°C with the effects of hyperthermia on steroidogenesis evaluated following stimulation with forskolin and ANGII. Cell death, protein/mRNA expression of steroidogenic enzymes and damage markers (HSP70/90), and steroid secretion were analyzed immediately and 7 days after treatment. Following treatment with hyperthermia, 42°C and 45°C did not induce cell death and were deemed sublethal doses while ≥50°C caused excess cell death in adrenal cells. Sublethal hyperthermia (45°C) caused a significant reduction in cortisol secretion immediately following treatment while differentially affecting the expression of various steroidogenic enzymes, although recovery of steroidogenesis was evident 7 days after treatment. As such, sublethal hyperthermia, which occurs in the transitional zone during thermal ablation induces a short-lived, unsustained inhibition of cortisol steroidogenesis in adrenocortical cells in vitro.

Disorders of Sex Development of Adrenal Origin.

Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.

The importance of sleep in selected diseases

Introduction: There are specific differences in physiological and biochemical processes during sleep. Adenosine and melatonin are involved in the regulation of circadian rhythms. During sleep, you can observe the secretion of growth hormone, a reduction in cortisol secretion, and a decrease in muscle tone and blood pressure. Sleep can have a major impact on the development of systemic diseases.Aim of the study: A review of the literature aimed at identifying selected negative factors influencing the quality of sleep and systemic diseases which are related to sleep disorders.State of knowledge: Factors that negatively affect sleep include stress, as well as excessive time spent in front of light-emitting screens. Long-term lack of sleep increases the risk of obesity, diabetes, cardiovascular diseases and psychiatric diseases. Summary: Sleep plays an important role in the proper functioning of the body. Its quality is affected by many factors. Sleep disorders can be both the effect and cause of many diseases. Especially in diagnosing psychiatric diseases, attention should be paid to the occurrence of sleep disorders.

The effect of neurostimulation applied to the left dorsolateral prefrontal cortex on post-stress adaptation as a function of depressive brooding

Depressive brooding following a stressful event predicts negative affect and neuroendocrine responses related to psychological stress. The dorsolateral prefrontal cortex (DLPFC) has been associated with the top-down regulation of thoughts and emotions, and abnormal neural activity within this region has been associated with increased psychological stress and ruminative thinking. The aim of this study was to investigate whether the modulation of the DLPFC could have beneficial effects on ruminative thoughts and the endocrine response following a self-relevant stressor. Using a sham-controlled within-subjects crossover-design, two sessions of intermittent theta-burst stimulation (iTBS) were administered over the left DLPFC to thirty-eight healthy-volunteers after they were confronted with a social-evaluative stressor, the Trier Social Stress Test. To assess stress recovery, momentary rumination was measured before and after a resting period subsequent to the encounter with the stressor. In addition, cortisol levels were measured between and after the two iTBS sessions that were applied during the stress recovery phase. Overall, iTBS did not significantly influence ruminative thinking and cortisol secretion during the stress recovery phase. However, taking into account participants ruminative tendencies, our results revealed that for participants with higher levels of brooding ruminative thinking remained stable after iTBS, whereas in the sham condition there was a marginal significant increase in ruminative thinking. Moreover, only after iTBS, there was a significant reduction in cortisol secretion (i.e. a faster return to baseline as compared to sham) for high brooders during the recovery from the stressor. These results show that the prefrontal cortex plays a role in stress recovery mechanisms in individuals who are more vulnerable for psychopathology.

The influence of personality on the effect of iTBS on cortisol secretion in stressed healthy females

It has been proposed that personality dimensions may be used to predict the response to repetitive Transcranial Magnetic Stimulation (rTMS) at the individual level. However, the underlying physiological mechanisms as to how personality may influence the effect of rTMS remains to be clarified. In this sham-controlled proof-of-concept study, we investigated whether personality features (assessed using the Temperament and Character Inventory) influence the effect of intermittent theta burst stimulation (iTBS) on the regulation of the hypothalamic-pituitary-adrenal axis. Thirty-eight healthy females received two sessions of iTBS over the left dorsolateral prefrontal cortex (DLPFC) after being stressed by the Trier Social Stress Test. Mood and salivary cortisol were assessed throughout the experimental protocol. We found overall no differences in the total cortisol secretion and the cortisol response to stress between the active and sham iTBS sessions. When taking into account personality features, our results show that when two sessions of iTBS over the left DLPFC are applied in stressed healthy females, a reduction in cortisol secretion is observed in individuals scoring higher in Cooperativeness. Our observations shed further light on the understanding of the influence of personality characteristics in the clinical outcome of rTMS in stress-related disorders.

Reduced hair cortisol after maltreatment mediates externalizing symptoms in middle childhood and adolescence.

The enduring impact of childhood maltreatment on biological systems and ensuing psychopathology remains incompletely understood. Long-term effects of stress may be reflected in cumulative cortisol secretion over several months, which is now quantifiable via hair cortisol concentrations (HCC). We conducted a first comprehensive investigation utilizing the potential of hair cortisol analysis in a large sample of maltreated and nonmaltreated children and adolescents. Participants included 537 children and adolescents (3-16years; 272 females) with maltreatment (n=245) or without maltreatment histories (n=292). Maltreated subjects were recruited from child protection services (CPS; n=95), youth psychiatric services (n=56), and the community (n=94). Maltreatment was coded using the Maltreatment Classification System drawing on caregiver interviews and complemented with CPS records. Caregivers and teachers reported on child mental health. HCC were assessed in the first 3cm hair segment. Analyses uniformly supported that maltreatment coincides with a gradual and dose-dependent reduction in HCC from 9 to 10years onwards relative to nonmaltreated controls. This pattern emerged consistently from both group comparisons between maltreated and nonmaltreated subjects (27.6% HCC reduction in maltreated 9-16-year-olds) and dimensional analyses within maltreated subjects, with lower HCC related to greater maltreatment chronicity and number of subtypes. Moreover, both group comparisons and dimensional analyses within maltreated youth revealed that relative HCC reduction mediates the effect of maltreatment on externalizing symptoms. From middle childhood onwards, maltreatment coincides with a relative reduction in cortisol secretion, which, in turn, may predispose to externalizing symptoms.

Changes in cortisol secretion and cognitive improvement during antidepressive treatment in patients with major depression: a longitudinal study

Cognitive deficits and elevated cortisol are characteristic features of depression. Only few studies have longitudinally examined the association between reduction in cortisol secretion during treatment and improvement of cognition in depressed patients and have come to inconclusive results. Cognitive function was longitudinally examined in 52 patients with major depression (mean age = 35 ± 11 years, Hamilton Depression Rating Scale mean score = 27 ± 5) before and after 3 weeks of standardized selective serotonin reuptake inhibitor (SSRI) treatment. Salivary cortisol levels were measured on the same days at 8:00, 12:00, 16:00 and 22:00 h. A healthy control group (n = 50) matched for age, gender and years of education was examined using the same measures and time points. SSRI treatment significantly reduced salivary cortisol in patients to levels of healthy controls (repeated-measures ANCOVA, time × group interaction p = .05). In patients, reduction of cortisol correlated with improvement in cognitive function in several domains: verbal memory (r = .26, p = .09), speed of information processing (r = .50, p < .01), cognitive set-shifting (r = .34, p = .03), visuoconstruction (r = -.28, p = .07), working memory (r = .27, p = .08), and attention (r = -.25, p = .10). This was confirmed in sex- and age-adjusted linear regression analyses. Improvement of cognitive function in patients with major depression during SSRI treatment was strongly related to decreased cortisol secretion.

DNA sequence variants of the FKBP5 gene are associated with unipolar depression

FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested to play a role in the regulation of the hypothalamic-pituitary-adrenocortical system and the pathophysiology of depression. Previously, three studies identified single nucleotide polymorphisms (SNPs) in the FKBP5 gene associated with response to antidepressants, and one study found an association with diagnosis of depression. We selected five markers from the region of interest. A case-control sample comprising 268 German in-patients with recurrent unipolar depression, and 284 German controls recruited from the general population were available. Association of the selected FKBP5 sequence variants with clinical depression were analysed. In addition, we explored association with treatment response by (a) the Hamilton Depression Rating Scale and (b) the dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test, as well as association with hippocampal volumes in a subpopulation of 110 patients. For three of the five investigated SNPs we were able to show association with the diagnosis of depression. In the subpopulation of 110 patients, diagnosis-related alleles were also associated with the reduction of cortisol secretion in the Dex/CRH test during a 4-wk treatment period, while psychopathological changes were not associated. Furthermore, diagnosis-related alleles were associated with reduction of the hippocampal volume. This study extends the replicated association of a promoter SNP with antidepressant response on a biological level by demonstrating normalization of the cortisol response under Dex/CRH stimulation during treatment. Furthermore, several of the investigated SNPs were associated with the disease status and the intermediate phenotype of hippocampal volume.

Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass: II. The effects on adrenal secretion of cortisol

Previous studies have indicated that a significant reduction in plasma cortisol levels occurs during nonpulsatile cardiopulmonary bypass as a result of adrenocorticol hypofunction. The Stöckert pulsatile pump system described in Part I has been employed in a comparative study of plasma cortisol levels in 20 patients subjected to pulsatile or nonpulsatile perfusion during open-heart surgery. The plasma cortisol response pattern in the nonpulsatile group was identical to the pattern previously described, with no significant rise in cortisol levels during the period of perfusion. In the pulsatile group, however, plasma cortisol levels rose significantly during perfusion, reaching a mean level at the end of perfusion which was highly significantly greater than that in the nonpulsatile group (p less than 0.001). Correction of the plasma cortisol values for the effect of hemodilution was performed and, again, corrected cortisol values indicated a highly significant increase in end-bypass levels in the pulsatile groups (p less than 0.001). These results clearly indicate that the reduction in cortisol secretion during nonpulsatile bypass may be prevented by the use of pulsatile perfusion.

The role of cortisol and growth hormone in the counter-regulation of insulin-induced hypoglycemia.

Four normal volunteers underwent a control insulin tolerance test (ITT) and an insulin tolerance test (ITT) after two days administration of the serotonin antagonist cyproheptadine (Cypro). Cypro administration resulted in an 81 +/- 11.4% (M +/- SEM) reduction in cortisol secretion and a 73 +/- 15.1% reduction in growth hormone (GH) secretion. Despite the reduction in hypoglycemia-induced cortisol and GH secretion, there was a similar decline and recovery of plasma glucose in the control ITT and the ITT after Cypro administration. Although previous studies indicate that normal basal levels of cortisol and growth hormone are needed for normal counter-regulation after insulin-induced hypoglycemia, augmented secretion of these hormones is probably not essential for this response. Hypoglycemia-induced increases in epinephrine and glucagon, secretion may contribute to the restoration of the normal plasma glucose concentration after insulin-induced hypoglycemia.

Adrenocortical response during corrected and uncorrected hypercapnic acidosis.

Adrenal venous flow rate and cortisol synthesis have been measured in dogs subjected to hypercapnic acidosis before and after intravenous administration of 0.34 mm/kg of tris (hydroxymethyl) amino methane (THAM). A comparison was made of adrenal venous, peripheral venous, and arterial blood, pH, pCO2 and O2 saturation. During uncorrected hypercapnic acidosis the concentration of cortisol increased while adrenal venous flow rate decreased, but there was a significant increase in the minute output of cortisol. With the concomitant administration of 0.34 mM/kg THAM, adrenal venous flow rate doubled. However, since this enhanced flow rate was accompanied by a sharp reduction in cortisol secretion, the minute output of cortisol returned to control levels. The possibility of a direct effect of THAM on the adrenal vascular bed and synthetic processes is discussed. Throughout all the above experiments adrenal venous blood resembled arterial blood rather than peripheral blood in its pCO2, O2 saturation and pH.