Acute stress exposure causes permissive effect of glucorticoids for vasopressin, allowing for increased blood pressure, affecting vascular smooth muscle endothelium directly and indirectly. Under normal stress exposure, cortisol permits vascular reactivity to angiotensin II and norepinephrine, as well. Glucocorticoids have a direct effect on induction of sodium and potassium ATPase in myocardial cells and tissue, resulting in increased inotrophy. (DeGroot 1648) Over time, the increase in cardiac effort will result in myocardial hypertrophy.
Chronic exposure to glucocorticoids correlates to hypertension, in part due to coincident increase in levels of mineralocorticoids, also released during periods of cortical stimulation. Chronic exposure of target tissues to glucocorticoids increases permissive action of on vasoconstriction agents, such as vasopressin. Long-term uncontrolled hypertension secondary to glucocorticoid excess is likely to be present with arteriosclerosis and result in tertiary renal insufficiency, CHF, cardiac hypertrophy, and/or CVA. (Marieb 737-8)
CNS Function
�Alterations in HPA axis functioning are associated with a number of psychiatric disorders and personality characteristics�overactivity and underactivity�are associated with depressive mood states, aggression, and lack of behavioral control.� (Adinoff 69) �One of the major disorders characteristic of an overactive HPA axis is melancholic depression�people with depression have a blunted ability to �counterregulate (SIC),� or adapt to negative feedback of increases in cortisol�this produces constant anxiety and overreaction to stimulation, followed by the paradoxical response called �learned helplessness,� in which victims�lose all motivation.� (NIH)
The hippocampus, as does the rest of the brain, contains copious numbers of glucocorticoid and mineralocorticoid receptors. Glucocorticoids can bind to either receptor type. The exact function of each type of receptor is still unclear. What is recognized is that when mineralocorticoid receptors are activated by glucocorticoids, in an environment of low glucocorticoid, the result is increased neuron activity, (DeGroot 1649) with enhanced memory and quickening of thought processes. This might help to explain vivid memory surrounding periods of intense and acute exposure to a stress stimulus. Glucocorticoids can also bind to their own receptors, however, and in the presence of excess or prolonged glucocorticoid exposure, studies have found that the occupation of these receptors by glucocorticoid will result in decreased neuronal activity. (DeGroot 1649) This would help to explain the inability to concentrate or retain memory during periods of prolonged stress or exposure to glucocorticoids. It may even lend some evidence to stress-related amnesia.
�Excess cortisol also impairs the brain�s ability to metabolize energy, which can leave the brain vulnerable to low levels of oxygen�long-term damage to the hypocampus�a brain structure vital to learning, memory, and the regulation of HPA axis function�appears to occur in chronic medical and psychiatric illnesses associated with persistently elevated levels of cortisol.� (Adinoff 69) Corticosteroids have been implicated in neuronal death. Researcher Ben Best states in his thesis, Mechanisms of Aging, that, �Evidence suggests an inverted U-shaped relationship between cortisol & cognition -- and that sustained higher cortisol levels can lead to a non-Alzheimer's dementia in humans,� and, �According to the glucocorticoid cascade hypothesis, glucocorticoid steroid hormones show rising blood levels with age, which increasingly damages feedback inhibition neurons in the hippocampus, resulting in even greater increases of blood glucocorticoid and a destructive feedback loop. Glucocorticoid hormone (cortisol in humans) is a normal response to stress, which mobilizes blood glucose and depresses the immune/inflammatory response, among other effects. Although useful in emergencies, chronic stress can be� (Pacific salmon use glucocorticoids to self-destruct after spawning).�
Other
In bone and skin, protein catabolism from muscle and bone takes place, as glucocorticoids cause the conversion of protein to glucose (Marieb 635). Cells within developing tissue have receptors for Insulin-like Growth Factor 1 (IGF-1). This factor is necessary for normal growth. These receptors are inhibited by cortisol during periods of prolonged stress. Research has shown that children with Cushing�s syndrome are, on average, 7.5-8 cm shorter than non-Cushing counterparts. Premature birth increases risk for growth retardation, likely due to extended stress of hospitalization and its effects on the HPA.
Growth-retarded fetuses have higher levels of CRH, ACTH, and cortisol which is attributed to stress in-utero or maternal stress hormone elevation. There is also evidence that stress of emotional deprivation and psychological harassment can result in a condition known as �Psychological Short Stature Syndrome,� characterized by delayed onset of physical maturity. This was originally noticed in infants in orphanages who failed to thrive and grow, but once placed in attention-filled caring environments resumed their growth pattern. In the laboratory setting, monkeys also display PSS syndrome when subjected to decreased attention and care. (NIH)
Stress stimulus following an initial stress is in some way facilitated so that the magnitude of the ACTH response to the subsequent stimulus is not diminished, despite feedback loop �inhibition due to elevated glucocorticoid levels produced by the first stress.� DeGroot explains that in sheep subjects, �dexamethasone blocks the response to hypoglycemia at both pituitary and hypothalamic levels, but blocks the response to an audiovisual stress only at the pituitary level.� (DeGroot 1645) This suggests that, although the pituitary response to audiovisual stress stimulus is blocked by the presence of dexamethasone, the hypothalamus is still activated by the audiovisual cue and not stimulated by an internal stressor (i.e.: hypoglycemia cue), allowing for activation of the sympathetic nervous system via other hypothalamic-derived stress hormones, like ADH, Vasopressin, and CRH
Cushing�s Syndrome
Cushing�s Syndrome is defined as, "a constellation of clinical abnormalities due to chronic exposure to excesses of cortisol (the major adrenocorticoid) or related corticosteroids." (Merck 106) "Cushing�s syndrome is the occurrence of clinical abnormalities associated with glucocorticoid excess secondary to exaggerated adrenal cortisol production or chronic glucocorticoid therapy...Cushing's disease is Cushing's Syndrome caused by pituitary ACTH excess." (Ferris 244) There are two types of Cushing�s syndrome, depending on the source of increased ACTH or glucocorticoid. These are exogenous and exogenous. The latter is further subdivided into two sub groups, as discussed below.