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The Adrenal Glands And Stress


The Adrenal Glands And Stress
The adrenal glands are located just above each kidney (hence the name; Fig. 49a) and consist of two endocrine tissues of distinct developmental origins. The inner core (the adrenal medulla) releases the catecholamine hormones adrenaline (epinephrine) and noradrenaline (norepinephrine). It develops from neuronal tissue and is functionally part of the sympathetic nervous system (Chapter 7). The outer layers of the gland (the adrenal cortex) originate from mesodermal tissue and secrete steroid hormones, primarily under the control of the anterior pituitary gland (Chapter 44). Removal of the adrenal glands in animals results in death within a few days, which is thought to result from the loss of the ability to cope with stress.


The Adrenal Glands And Stress

The adrenal medulla
The chromaffin cells of the adrenal medulla manufacture and secrete noradrenaline (20%) and adrenaline (80%). These catecholamine hormones are derived from tyrosine by a series of steps catalysed by specific enzymes (Fig. 49b). The production of the rate-limiting enzyme, phenylethanolamine-N-methyl transferase, is stimulated by cortisol, providing a direct link between the functioning of the medulla and cortex. The secretion of catecholamines is stimulated by sympathetic preganglionic neurones located in the spinal cord (Chapter 7), so that the adrenal medulla functions in concert with the sympathetic nervous system, of which noradrenaline is the main neurotransmitter. Catecholamine release contributes to normal physiological functions, but is enhanced by stress (see below). Adrenaline and noradrenaline act through guanosine triphosphate-binding protein (G-protein)-coupled adrenoceptors. These are classified as α1, α2 and β1–β3. The hormones have the same effects in tissues as the stimulation of sympathetic nerves, with important stress-related responses being vasoconstriction (α1), increased cardiac output (β1) and increased glycolysis and lipolysis (β2, β3). These actions support increased physical activity. Noradrenaline has equal potency at all adrenoceptors, but adrenaline, at normal plasma concentrations, will only activate β-receptors (NB: higher levels do stimulate α-receptors). Phaeochromocytoma is a tumour of the adrenal medulla that leads to the excess production of catecholamines, with high blood pressure as the most immediately threatening symptom. It is treated by α-adrenoceptor antagonists and/or surgery.

The adrenal cortex
The cortex is made up of three zones of tissue: the outer zona glomerulosa, which releases aldosterone; the zona fasciculata, which produces cortisol and several related but less important hormones; and the inner zona reticularis, which secretes the androgen dehydroepiandrosterone (DHEA). All of these secretions are steroids (Fig. 49c). Aldosterone is referred to as a mineralocorticoid as it controls the reabsorption of Na+ and K+ ions in the kidney (Chapter 35), whereas DHEA and its metabolite, androstenedione, provide an important source of androgens for females, contributing to hair growth and libido (Chapter 50). Cortisol and its analogues (such as cortisone) have powerful effects on glucose metabolism and are collectively classified as glucocorticoids, although they do have some mineralocorticoid actions. The release of cortisol and DHEA is stimulated by adrenocorticotrophic hormone (ACTH) liberated from the pituitary gland (Chapter 44; Fig. 49d), whereas the secretion of aldosterone is stimulated by angiotensin II (Chapter 35). The effects of cortisol are mediated by intracellular receptors that translocate to the cell nucleus after binding the hormone. The cortisol–receptor complex binds to glucocorticoid response elements on deoxyribonucleic acid (DNA) to initiate gene transcription.
Cortisol is released during the course of normal physiological activity. The pattern of secretion is pulsatile, driven by activity in corticotrophin-releasing hormone (CRH) neurones of the hypothalamus (Chapter 44). There is usually a surge in cortisol release in the hour after waking. The primary stimulus for the increased release of glucocorticoids is stress, which is the result of exposure to adverse situations. The stress response is driven by the amygdala, part of the forebrain that stimulates: (i) activity in hypothalamic CRH neurones; (ii) activity in the sympathetic nervous system; (iii) activity in the parasympathetic nerves that cause acid secretion in the stomach (Chapter 38); and (iv) the feeling of fear (Fig. 49d). The stress response evolved to cope with immediate threats, such as predators, to which the appropriate physiological reaction is to prepare for physical activity. The actions of the two parts of the adrenal gland are complementary in this respect. Catecholamines are released from the medulla to produce a rapid increase in cardiac output and the mobilization of metabolic fuels. Corticosteroids produce a slower, more sustained response, increasing the amount of glucose in the plasma (Chapter 43) by: (i) increasing glycolysis and gluconeogenesis in the liver (Chapter 40); (ii) reducing glucose transport into storage tissues; (iii) increasing protein catabolism with a consequent release of amino acids from all tissues other than the liver; and (iv) increasing the mobilization of lipids from adipose tissue. High levels of glucocorticoids also suppress the activity of immune cells to produce an anti-inflammatory effect, and can mimic the actions of aldosterone on the kidney to retain Na+ and lose K+ ions. The stress response is appropriate as long as the stress is relieved promptly. Unfortunately, modern life places many of us in positions in which stress is prolonged. This can lead to chronic hypertension, gastric ulceration, immunosuppression and depression (Fig. 49d). Glucocorticoid derivatives, such as dexamethasone, are widely used as anti-inflammatory agents in conditions such as arthritis and asthma. Chronically high levels of glucocorticoids eventually cause weakening of the skin, muscle wasting, reduction in bone strength, increased rates of infection due to immunosuppression, and can damage nerve cells in the hippocampus that are part of a feedback circuit controlling responses to stress (Fig. 49d). Thus, the long-term therapeutic use of steroids must be very carefully monitored, especially in the young where normal growth may be affected. Diseases of the adrenal cortex include Cushing’s syndrome, which results from the excessive release of glucocorticoids and has a range of symptoms similar to those described above, and Addison’s disease, which is the result of adrenocortical hypoactivity and is characterized by symptoms of hypoglycaemia, weight loss and skin pigmentation.