Cortisol release

Pearce G.P. and Patterson A.M. (1992). Physical contact with the boar is required for maximum stimulation of puberty in the gilt because it allows transfer of boar pheromones and not because it induces cortisol release. Anim Reprod Sci 27, 209-224. 

Antonijevic, I. A., Murck, H., Bohlhalter, S. et al. (2000). Neuropeptide Y promotes sleep and inhibits ACTH and cortisol release in young men. Neuropharmacology 39, 1474-81. 

Frieboes, R. M., Murck, H., Maier, P. et al. (1995). Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man. Neuroendocrinology 61, 584-9. 

Nissen, E., Uvnas-Moberg, K., Svensson, K., Stock, S, Widstrom, A. M., and Winberg, J. 1996. Different patterns of oxytocin, prolactin but not cortisol release during breast feeding in women delivered by caesarean section or by the vaginal route. Early Human Development, in press. 

Indicative of serotonergic dysfunction, abused children with depression were shown to exhibit increased prolactin, but normal cortisol responses to the injection of E-5-hydroxytryptophan, a precursor of 5-HT, as compared to nonabused depressed children and controls (Kaufman et ah, 1998). Likewise, increased prolactin responses to fenfluramine were observed in boys with adverse rearing environment (Pine et ah, 1997). Since prolactin, but not cortisol release, is mediated via 5-HTia receptors, these findings suggest sensitization of these receptors due to early-life stress. Another study recently reported that children with traumatic brain injury (TBl) who had experienced abuse have dramatic increases in CSE concentrations of glutamate, compared to nonabused TBI children (Ruppel et ah, 2001). 

Rohatagi S, Krishnaswami S, Pfister M, Sahasranaman S. Model-based covariate pharmacokinetic analysis and lack of cortisol suppression by the new inhaled corticosteroid ciclesonide using a novel cortisol release model. Am J Ther... 

Hergovich N, Singer E, Agneter E, Eichler HG, Graselli U, Simhandl C, Jilma B. Comparison of the effects of ketamine and memantine on prolactin and cortisol release in men. a randomized, double-blind, placebo-controlled trial. Neuropsychopharmacology 2001 24(5) 590-3. 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

In determining cortisol in serum, most of the cortisol is bound to corticosteroid-binding globulin and other serum proteins. How then is cortisol released for detection [1006] (2 marks)... 

For further progress towards mechanisms based models, such phenomenological descriptions shall also be examined in context with disease-related disturbances of autonomous functions. This mainly concerns disturbances of sleep-wake cycles and cortisol release which are the most reliable biological markers of mental diseases, especially major depression, and can provide objective and quantifiable parameters (e.g. EEG frequency components, cortisol blood level) for the estimation of an otherwise mainly subjective and only behaviorally manifested illness. Moreover, there is a manifold of data which interlink the alterations of the autonomous system parameters (sleep states, cortisol release) with alterations of neural dynamics. Therefore, the most promising approach also to understand the interrelations between neural dynamics and affective disorders probably goes via the analysis of mood related disturbances of autonomous functions. 

Autonomous functions, especially the circadian rhythms of sleep-wake cycles and cortisol release, are significantly disturbed during depression. However, it is still unclear whether these circadian alterations are reliably linked with psychopathology and whether they provide clues to the underlying mechanism, in particular with respect to the neurotransmitter models of depression [8] and the CRH-overdrive hypothesis [29]. 

Hypercortisolism in depression is the peripheral indicator of a general disturbance of the entire stress regulation. A primary reason for the enhanced cortisol release is obviously a central hypersecretion of CRH at the hypothalymic site [29, 31, 32]. The consequence of CRH hypersecretion is not only an increased cortisol level but also a down -regulation of glucocorticoid and mineralocorticoid receptors at the level of the pituitary and the hippocampus [33], i.e. a disturbance of the feedback system. 

Fig. 7.6 Computer simulations of circadian cortisol release, (a) Activation curves of the positive (MR) and negative (GR) feedback loops of cortisol to diverse brain areas (see Fig. 6.5) via mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), respectively. In combination (MR-GR), there is...

In mental disorders, in contrast to other neural diseases like epilepsy or Parkinson s disease, not much is known about the relevant alteration of neural dynamics. It can be just assumed from the pa lien I s inappropriate environmental responsiveness that neuronal adaptability and flexibility are disturbed, accompanied by a changed neuronal sensitivity on external stimuli. Fortunately, there is more information with regard to the neural control of sleep-wake cycles and cortisol release, which are very reliable biological markers of mental disorders and therefore may provide a link for a better understanding also of the neuronal dynamics which control mood. 

We have emphasized the fact that the progression of mental diseases, especially major depression, is associated with significant disturbances in the circadian rhythms of autonomous functions, especially sleep-wake cycles and hormone release. These rhythms are naturally occurring but are distorted in affective disorders. The most clear distortions are often seen in the ultradian components in specific phases of the circadian cycle, e.g. in the morning peak of cortisol release or in the REM to nonREM transition during the sleep state. 

We have considered that all these systems are under neuronal control. While the relation between neural activity and different mood states is unknown so far, it is well established that physiologically relevant transitions in autonomous functions like sleep-wake cycles and cortisol release are associated with signifi-... 

We have shown computer simulations from all these different levels First, we modeled the time course of affective disorders and showed that clinical observation can be mimicked in remarkable details with a combination of oscillatory dynamics and noise. Second, we presented an initial, still very basic, model of circadian cortisol release which nevertheless provided new insights also into eventual disease relevant alterations. Third, we showed single neuron and neuronal network simulations to elucidate the relevant interdependencies between ionic conductances and network interactions with regard to neuronal synchronization at different dynamic, also heterogeneous states. 

The complete system responses are determined by the interactions, i.e. resonances, between the subthreshold and event-generating mechanisms. Again, in the HPA axis model, these interactions, so far, are rather simple and unidirectional. The circadian pacemaker modulates the H PA feedback loops in a nonlinear multiplicative way but is itself not influenced by the dynamics of the cortisol releasing processes. In contrast, in the neuronal and psychiatric models, the two subsystems are interlinked by a common control variable, the membrane voltage and the disease variable, respectively. These interlinks are a major source of very complex, inclusively chaotic dynamics [96, 111, 112]. 

Cushing s syndrome is caused by the hypersecretion of cortisol by cells in the adrenal cortex. Hypersecretion can be due to overstimulation of cortisol-releasing mechanisms by excess ACTH, a pituitary hormone. Cushing s can result from pituitary or adrenal tumors. It is further characterized by obesity, a rounded face, muscle weakness, a tendency to bruise easily, and numerous other complications. 

Jezova D, Duncko R, Lassanova M, Kriska M, Moncek F. Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EBg 761) in healthy volunteers. J Physiol Pharmacol 2002 53 337-348. 

Normal circulating levels of cortisol, including the circadian early-morning rise and the moderate elevations after meals and minor stresses, help sustain basic physiological (vegetative) functions. Large amounts of cortisol released in response to major stresses enable the individual to withstand, or cope with, the metabolic, cardiovascular. 

---