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Papers by Türkan Yurtsever

Research paper thumbnail of Temporal dynamics of cortisol-associated changes in mRNA expression of glucocorticoid responsive genes FKBP5, GILZ, SDPR, PER1, PER2 and PER3 in healthy humans

Psychoneuroendocrinology, 2018

Secretion of the stress hormone cortisol follows a circadian rhythm and is stimulated following s... more Secretion of the stress hormone cortisol follows a circadian rhythm and is stimulated following stress exposure. Cortisol regulates the transcription of several genes, primarily through activation of the glucocorticoid receptor (GR). Previously, we showed an upregulation of PERIOD genes PER1 and PER3 after pharmacological/glucocorticoid challenge in vivo and in vitro. The current study aims to investigate the temporal association between unstimulated, diurnal cortisol secretion and the expression of selected GR-target genes (PER1, PER2, PER3, FKBP5, GILZ and SDPR) in vivo to determine the timing of the most pronounced coupling between cortisol and mRNA expression. Unstimulated plasma and saliva cortisol concentrations and gene expression levels in whole blood were measured every 15 min from early morning until 16:00 h in 18 healthy men. Time-lagged correlations of cortisol concentrations with mRNA expression levels were assessed allowing lags between -240 and + 240 min. Strong positive correlations at non-zero lags between cortisol levels and the expression of FKBP5 (plasma: r = 0.74 (CI = 0.65-0.81), p < 0.001, lag + 90 min; saliva: r = 0.71 (CI = 0.61-0.78), p < 0.001, lag + 75 min), and GILZ (plasma: r = 0.59 (CI = 0.46-0.69), p < 0.001, lag + 30 min; saliva r = 0.53 (CI = 0.41-0.63), p < 0.001, lag +15 min) were observed. Expressions of PERIOD genes and SDPR correlated only weakly with cortisol (all |r| < 0.25). Our findings demonstrate strong correlations between cortisol secretion and gene expression in humans under unstimulated conditions. The observed time-lags can guide future research aiming to characterize glucocorticoid-dependent gene expression in clinical samples with stress-related disorders.

Research paper thumbnail of The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects

The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects

Chronobiology international, Jan 2, 2016

The physiological stress system and the circadian clock system communicate with each other at dif... more The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression. Forty participants (50% males and 50% females) were randomly assigned to groups receiving a saline placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was drawn every 15 min to measure quantitative gene expression of PER1, PER2 and PER3. A potential role of the GR was determined by an ex vivo study stimulating whole blood with hydrocortisone and RU486 (a GR antagonist). As a result, moderate doses of hydrocortisone produced an acute an...

Research paper thumbnail of Interaction Between the Hypothalamic-Pituitary-Adrenal Axis and Behavioural Compensation Following Unilateral Vestibular Deafferentation

Interaction Between the Hypothalamic-Pituitary-Adrenal Axis and Behavioural Compensation Following Unilateral Vestibular Deafferentation

Acta Oto-Laryngologica, 2003

Vestibular compensation is defined as the process of behavioural recovery that occurs following t... more Vestibular compensation is defined as the process of behavioural recovery that occurs following the loss of sensory input from one or both vestibular labyrinths. The visual and postural instability resulting from the vestibular damage must alter the homeostasis of the subject; however, very little research has been conducted that investigates the interaction between vestibular compensation and the adaptive stress response of the body, i.e. the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this review is to describe and evaluate the experimental evidence indicating a link between vestibular compensation and the body&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s response to stress, via the HPA axis.

Research paper thumbnail of Temporal dynamics of cortisol-associated changes in mRNA expression of glucocorticoid responsive genes FKBP5, GILZ, SDPR, PER1, PER2 and PER3 in healthy humans

Psychoneuroendocrinology, 2018

Secretion of the stress hormone cortisol follows a circadian rhythm and is stimulated following s... more Secretion of the stress hormone cortisol follows a circadian rhythm and is stimulated following stress exposure. Cortisol regulates the transcription of several genes, primarily through activation of the glucocorticoid receptor (GR). Previously, we showed an upregulation of PERIOD genes PER1 and PER3 after pharmacological/glucocorticoid challenge in vivo and in vitro. The current study aims to investigate the temporal association between unstimulated, diurnal cortisol secretion and the expression of selected GR-target genes (PER1, PER2, PER3, FKBP5, GILZ and SDPR) in vivo to determine the timing of the most pronounced coupling between cortisol and mRNA expression. Unstimulated plasma and saliva cortisol concentrations and gene expression levels in whole blood were measured every 15 min from early morning until 16:00 h in 18 healthy men. Time-lagged correlations of cortisol concentrations with mRNA expression levels were assessed allowing lags between -240 and + 240 min. Strong positive correlations at non-zero lags between cortisol levels and the expression of FKBP5 (plasma: r = 0.74 (CI = 0.65-0.81), p < 0.001, lag + 90 min; saliva: r = 0.71 (CI = 0.61-0.78), p < 0.001, lag + 75 min), and GILZ (plasma: r = 0.59 (CI = 0.46-0.69), p < 0.001, lag + 30 min; saliva r = 0.53 (CI = 0.41-0.63), p < 0.001, lag +15 min) were observed. Expressions of PERIOD genes and SDPR correlated only weakly with cortisol (all |r| < 0.25). Our findings demonstrate strong correlations between cortisol secretion and gene expression in humans under unstimulated conditions. The observed time-lags can guide future research aiming to characterize glucocorticoid-dependent gene expression in clinical samples with stress-related disorders.

Research paper thumbnail of The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects

The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects

Chronobiology international, Jan 2, 2016

The physiological stress system and the circadian clock system communicate with each other at dif... more The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression. Forty participants (50% males and 50% females) were randomly assigned to groups receiving a saline placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was drawn every 15 min to measure quantitative gene expression of PER1, PER2 and PER3. A potential role of the GR was determined by an ex vivo study stimulating whole blood with hydrocortisone and RU486 (a GR antagonist). As a result, moderate doses of hydrocortisone produced an acute an...

Research paper thumbnail of Interaction Between the Hypothalamic-Pituitary-Adrenal Axis and Behavioural Compensation Following Unilateral Vestibular Deafferentation

Interaction Between the Hypothalamic-Pituitary-Adrenal Axis and Behavioural Compensation Following Unilateral Vestibular Deafferentation

Acta Oto-Laryngologica, 2003

Vestibular compensation is defined as the process of behavioural recovery that occurs following t... more Vestibular compensation is defined as the process of behavioural recovery that occurs following the loss of sensory input from one or both vestibular labyrinths. The visual and postural instability resulting from the vestibular damage must alter the homeostasis of the subject; however, very little research has been conducted that investigates the interaction between vestibular compensation and the adaptive stress response of the body, i.e. the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this review is to describe and evaluate the experimental evidence indicating a link between vestibular compensation and the body&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s response to stress, via the HPA axis.