adrenal gland adrenal gland the adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. they are found above the kidneys. each gland has an outer cortex which produces steroid hormones and an inner medulla. the adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis. adrenal glandthe adrenal glands lie above the kidneys.endocrine systemdetailsprecursormesoderm and neural crestsystemendocrine systemarterysuperior, middle and inferior suprarenal arteriesveinsuprarenal veinsnerveceliac and renal plexuslymphlumbar lymph nodesidentifierslatinglandula suprarenalismeshd000311ta98a11.5.00.001ta23874fma9604anatomical terminology the adrenal cortex produces three main types of steroid hormones: mineralocorticoids, glucocorticoids, and androgens. mineralocorticoids (such as aldosterone) produced in the zona glomerulosa help in the regulation of blood pressure and electrolyte balance. the glucocorticoids cortisol and cortisone are synthesized in the zona fasciculata; their functions include the regulation of metabolism and immune system suppression. the innermost layer of the cortex, the zona reticularis, produces androgens that are converted to fully functional sex hormones in the gonads and other target organs. the production of steroid hormones is called steroidogenesis, and involves a number of reactions and processes that take place in cortical cells. the medulla produces the catecholamines, which function to produce a rapid response throughout the body in stress situations. a number of endocrine diseases involve dysfunctions of the adrenal gland. overproduction of cortisol leads to cushing's syndrome, whereas insufficient production is associated with addison's disease. congenital adrenal hyperplasia is a genetic disease produced by dysregulation of endocrine control mechanisms. a variety of tumors can arise from adrenal tissue and are commonly found in medical imaging when searching for other diseases. structure adrenal glands, anterior (left) and posterior (right) surface. the adrenal glands are located on both sides of the body in the retroperitoneum, above and slightly medial to the kidneys. in humans, the right adrenal gland is pyramidal in shape, whereas the left is semilunar or crescent shaped and somewhat larger. the adrenal glands measure approximately 5 cm in length, 3 cm in width, and up to 1 cm in thickness. their combined weight in an adult human ranges from 7 to 10 grams. the glands are yellowish in colour. the adrenal glands are surrounded by a fatty capsule and lie within the renal fascia, which also surrounds the kidneys. a weak septum (wall) of connective tissue separates the glands from the kidneys. the adrenal glands are directly below the diaphragm, and are attached to the crura of the diaphragm by the renal fascia. each adrenal gland has two distinct parts, each with a unique function, the outer adrenal cortex and the inner medulla, both of which produce hormones. adrenal cortex main article: adrenal cortex section of human adrenal gland under the microscope, showing its different layers. from the surface to the center: zona glomerulosa, zona fasciculata, zona reticularis, medulla. in the medulla, the central adrenomedullary vein is visible. the adrenal cortex is the outer region and also the largest part of an adrenal gland. it is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. each zone is responsible for producing specific hormones. the adrenal cortex is the outermost layer of the adrenal gland. within the cortex are three layers, called "zones". when viewed under a microscope each layer has a distinct appearance, and each has a different function. the adrenal cortex is devoted to production of hormones, namely aldosterone, cortisol, and androgens. zona glomerulosa the outermost zone of the adrenal cortex is the zona glomerulosa. it lies immediately under the fibrous capsule of the gland. cells in this layer form oval groups, separated by thin strands of connective tissue from the fibrous capsule of the gland and carry wide capillaries. this layer is the main site for production of aldosterone, a mineralocorticoid, by the action of the enzyme aldosterone synthase. aldosterone plays an important role in the long-term regulation of blood pressure. zona fasciculata the zona fasciculata is situated between the zona glomerulosa and zona reticularis. cells in this layer are responsible for producing glucocorticoids such as cortisol. it is the largest of the three layers, accounting for nearly 80% of the volume of the cortex. in the zona fasciculata, cells are arranged in columns radially oriented towards the medulla. cells contain numerous lipid droplets, abundant mitochondria and a complex smooth endoplasmic reticulum. zona reticularis the innermost cortical layer, the zona reticularis, lies directly adjacent to the medulla. it produces androgens, mainly dehydroepiandrosterone (dhea), dhea sulfate (dhea-s), and androstenedione (the precursor to testosterone) in humans. its small cells form irregular cords and clusters, separated by capillaries and connective tissue. the cells contain relatively small quantities of cytoplasm and lipid droplets, and sometimes display brown lipofuscin pigment. medulla main article: adrenal medulla the adrenal medulla is at the centre of each adrenal gland, and is surrounded by the adrenal cortex. the chromaffin cells of the medulla are the body's main source of the catecholamines, such as adrenaline and noradrenaline, released by the medulla. approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine) are secreted here. the adrenal medulla is driven by the sympathetic nervous system via preganglionic fibers originating in the thoracic spinal cord, from vertebrae t5–t11. because it is innervated by preganglionic nerve fibers, the adrenal medulla can be considered as a specialized sympathetic ganglion. unlike other sympathetic ganglia, however, the adrenal medulla lacks distinct synapses and releases its secretions directly into the blood. blood supply the adrenal glands have one of the greatest blood supply rates per gram of tissue of any organ: up to 60 small arteries may enter each gland. three arteries usually supply each adrenal gland: the superior suprarenal artery, a branch of the inferior phrenic artery the middle suprarenal artery, a direct branch of the abdominal aorta the inferior suprarenal artery, a branch of the renal artery these blood vessels supply a network of small arteries within the capsule of the adrenal glands. thin strands of the capsule enter the glands, carrying blood to them. venous blood is drained from the glands by the suprarenal veins, usually one for each gland: the right suprarenal vein drains into the inferior vena cava the left suprarenal vein drains into the left renal vein or the left inferior phrenic vein. the central adrenomedullary vein, in the adrenal medulla, is an unusual type of blood vessel. its structure is different from the other veins in that the smooth muscle in its tunica media (the middle layer of the vessel) is arranged in conspicuous, longitudinally oriented bundles. variability the adrenal glands may not develop at all, or may be fused in the midline behind the aorta. these are associated with other congenital abnormalities, such as failure of the kidneys to develop, or fused kidneys. the gland may develop with a partial or complete absence of the cortex, or may develop in an unusual location. function different hormones are produced in different zones of the cortex and medulla of the gland. light microscopy at magnification × 204. the adrenal gland secretes a number of different hormones which are metabolised by enzymes either within the gland or in other parts of the body. these hormones are involved in a number of essential biological functions. corticosteroids corticosteroids are a group of steroid hormones produced from the cortex of the adrenal gland, from which they are named. mineralocorticoids such as aldosterone regulate salt ("mineral") balance and blood pressure glucocorticoids such as cortisol influence metabolism rates of proteins, fats and sugars ("glucose"). androgens such as dehydroepiandrosterone. mineralocorticoids the adrenal gland produces aldosterone, a mineralocorticoid, which is important in the regulation of salt ("mineral") balance and blood volume. in the kidneys, aldosterone acts on the distal convoluted tubules and the collecting ducts by increasing the reabsorption of sodium and the excretion of both potassium and hydrogen ions. aldosterone is responsible for the reabsorption of about 2% of filtered glomerular filtrate. sodium retention is also a response of the distal colon and sweat glands to aldosterone receptor stimulation. angiotensin ii and extracellular potassium are the two main regulators of aldosterone production. the amount of sodium present in the body affects the extracellular volume, which in turn influences blood pressure. therefore, the effects of aldosterone in sodium retention are important for the regulation of blood pressure. glucocorticoids cortisol is the main glucocorticoid in humans. in species that do not create cortisol, this role is played by corticosterone instead. glucocorticoids have many effects on metabolism. as their name suggests, they increase the circulating level of glucose. this is the result of an increase in the mobilization of amino acids from protein and the stimulation of synthesis of glucose from these amino acids in the liver. in addition, they increase the levels of free fatty acids, which cells can use as an alternative to glucose to obtain energy. glucocorticoids also have effects unrelated to the regulation of blood sugar levels, including the suppression of the immune system and a potent anti-inflammatory effect. cortisol reduces the capacity of osteoblasts to produce new bone tissue and decreases the absorption of calcium in the gastrointestinal tract. the adrenal gland secretes a basal level of cortisol but can also produce bursts of the hormone in response to adrenocorticotropic hormone (acth) from the anterior pituitary. cortisol is not evenly released during the day – its concentrations in the blood are highest in the early morning and lowest in the evening as a result of the circadian rhythm of acth secretion. cortisone is an inactive product of the action of the enzyme 11β-hsd on cortisol. the reaction catalyzed by 11β-hsd is reversible, which means that it can turn administered cortisone into cortisol, the biologically active hormone. formation steroidogenesis in the adrenal glands – different steps occur in different layers of the gland all corticosteroid hormones share cholesterol as a common precursor. therefore, the first step in steroidogenesis is cholesterol uptake or synthesis. cells that produce steroid hormones can acquire cholesterol through two paths. the main source is through dietary cholesterol transported via the blood as cholesterol esters within low density lipoproteins (ldl). ldl enters the cells through receptor-mediated endocytosis. the other source of cholesterol is synthesis in the cell's endoplasmic reticulum. synthesis can compensate when ldl levels are abnormally low. in the lysosome, cholesterol esters are converted to free cholesterol, which is then used for steroidogenesis or stored in the cell. the initial part of conversion of cholesterol into steroid hormones involves a number of enzymes of the cytochrome p450 family that are located in the inner membrane of mitochondria. transport of cholesterol from the outer to the inner membrane is facilitated by steroidogenic acute regulatory protein and is the rate-limiting step of steroid synthesis. the layers of the adrenal gland differ by function, with each layer having distinct enzymes that produce different hormones from a common precursor. the first enzymatic step in the production of all steroid hormones is cleavage of the cholesterol side chain, a reaction that forms pregnenolone as a product and is catalyzed by the enzyme p450scc, also known as cholesterol desmolase. after the production of pregnenolone, specific enzymes of each cortical layer further modify it. enzymes involved in this process include both mitochondrial and microsomal p450s and hydroxysteroid dehydrogenases. usually a number of intermediate steps in which pregnenolone is modified several times are required to form the functional hormones. enzymes that catalyze reactions in these metabolic pathways are involved in a number of endocrine diseases. for example, the most common form of congenital adrenal hyperplasia develops as a result of deficiency of 21-hydroxylase, an enzyme involved in an intermediate step of cortisol production. regulation negative feedback in the hpa axis glucocorticoids are under the regulatory influence of the hypothalamus-pituitary-adrenal (hpa) axis. glucocorticoid synthesis is stimulated by adrenocorticotropic hormone (acth), a hormone released into the bloodstream by the anterior pituitary. in turn, production of acth is stimulated by the presence of corticotropin-releasing hormone (crh), which is released by neurons of the hypothalamus. acth acts on the adrenal cells first by increasing the levels of star within the cells, and then of all steroidogenic p450 enzymes. the hpa axis is an example of a negative feedback system, in which cortisol itself acts as a direct inhibitor of both crh and acth synthesis. the hpa axis also interacts with the immune