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105-397: 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 ,

210-413: A diurnal rhythm. Aldosterone is the primary of several endogenous members of the class of mineralocorticoids in humans. Deoxycorticosterone is another important member of this class. Aldosterone tends to promote Na and water retention, and lower plasma K concentration by the following mechanisms: Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which

315-401: 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

420-407: A balance between secretion and degradation/ excretion . The liver and kidneys are the major organs that degrade hormones; breakdown products are excreted in urine and faeces. Hormone half-life and duration of activity are limited and vary from hormone to hormone. Interaction of hormones at target cells Permissiveness is the situation in which a hormone cannot exert its full effects without

525-413: 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

630-403: A different cell type nearby. The ability of a target cell to respond to a hormone depends on the presence of receptors, within the cell or on its plasma membrane, to which the hormone can bind. Hormone receptors are dynamic structures. Changes in the number and sensitivity of hormone receptors may occur in response to high or low levels of stimulating hormones. Blood levels of hormones reflect

735-439: A diurnal rhythm of release, which is subject to modification by stimuli influencing the hypothalamus. Somatotropic hormone or growth hormone (GH) is an anabolic hormone that stimulates the growth of all body tissues especially skeletal muscle and bone. It may act directly, or indirectly via insulin-like growth factors (IGFs). GH mobilizes fats, stimulates protein synthesis, and inhibits glucose uptake and metabolism. Secretion

840-514: A future need from interaction with a predator, since too high a serum content of potassium has very adverse effects on nervous transmission. Pressure-sensitive baroreceptors are found in the vessel walls of nearly all large arteries in the thorax and neck, but are particularly plentiful in the sinuses of the carotid arteries and in the arch of the aorta. These specialized receptors are sensitive to changes in mean arterial pressure. An increase in sensed pressure results in an increased rate of firing by

945-419: A mechanism protects the body from excess aldosterone receptor stimulation by glucocorticoids (such as cortisol), which happen to be present at much higher concentrations than mineralocorticoids in the healthy individual. The mechanism consists of an enzyme called 11 β-hydroxysteroid dehydrogenase (11β-HSD). This enzyme co-localizes with intracellular adrenal steroid receptors and converts cortisol into cortisone,

1050-420: 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 . 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

1155-453: 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 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

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1260-410: 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 are a group of steroid hormones produced from the cortex of the adrenal gland, from which they are named. The adrenal gland produces aldosterone , a mineralocorticoid , which is important in

1365-492: A platform for the production of a recurrent Ca channels signal that can be controlled by angiotensin II and extracellular potassium , the 2 major regulators of aldosterone production. Voltage-gated Ca channels have been detected in the zona glomerulosa of the human adrenal, which suggests that Ca channel blockers may directly influence the adrenocortical biosynthesis of aldosterone in vivo. The amount of plasma renin secreted

1470-446: A quickening of breathing and heart rate, an increase in blood pressure, and constriction of blood vessels in many parts of the body. Catecholamines are produced in chromaffin cells in the medulla of the adrenal gland, from tyrosine , a non-essential amino acid derived from food or produced from phenylalanine in the liver. The enzyme tyrosine hydroxylase converts tyrosine to L-DOPA in the first step of catecholamine synthesis. L-DOPA

1575-408: 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

1680-473: A relatively inactive metabolite with little affinity for the MR. Liquorice , which contains glycyrrhetinic acid , can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome. Angiotensin is involved in regulating aldosterone and is the core regulation. Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present. A small portion of

1785-440: A result of hypersecretion, loss of suppression, hyperplastic , or neoplastic change, or hyperstimulation. Endocrinopathies are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Secondary endocrine disease is indicative of a problem with the pituitary gland. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones. As

1890-449: A result of the dysregulation of hormone production (as in some types of Cushing's syndrome ) leading to an excess or insufficiency of adrenal hormones and the related symptoms. Cushing's syndrome is the manifestation of glucocorticoid excess. It can be the result of a prolonged treatment with glucocorticoids or be caused by an underlying disease which produces alterations in the HPA axis or

1995-418: A small amount of circulating noradrenaline. These hormones are released by the adrenal medulla, which contains a dense network of blood vessels. Adrenaline and noradrenaline act by interacting with adrenoreceptors throughout the body, with effects that include an increase in blood pressure and heart rate. Actions of adrenaline and noradrenaline are responsible for the fight or flight response , characterised by

2100-594: Is a family of congenital diseases in which mutations of enzymes that produce steroid hormones result in a glucocorticoid deficiency and malfunction of the negative feedback loop of the HPA axis . In the HPA axis, cortisol (a glucocorticoid) inhibits the release of CRH and ACTH , hormones that in turn stimulate corticosteroid synthesis. As cortisol cannot be synthesized, these hormones are released in high quantities and stimulate production of other adrenal steroids instead. The most common form of congenital adrenal hyperplasia

2205-401: Is abnormally increased levels of aldosterone, while hypoaldosteronism is abnormally decreased levels of aldosterone. A measurement of aldosterone in blood may be termed a plasma aldosterone concentration ( PAC ), which may be compared to plasma renin activity (PRA) as an aldosterone-to-renin ratio . Primary aldosteronism , also known as primary hyperaldosteronism , is characterized by

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2310-406: Is also able to perform an 18- oxidation . Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex ; 11β-hydroxylase is found in the zona glomerulosa and zona fasciculata . Aldosterone synthase is normally absent in other sections of the adrenal gland . Aldosterone synthesis is stimulated by several factors: The secretion of aldosterone has

2415-419: Is also affected to one extent or another by nervous control, which integrates the inverse of carotid artery pressure, pain, posture, and probably emotion (anxiety, fear, and hostility) (including surgical stress ). Anxiety increases aldosterone, which must have evolved because of the time delay involved in migration of aldosterone into the cell nucleus. Thus, there is an advantage to an animal's anticipating

2520-457: Is an effective screening test to screen for primary hyperaldosteronism related to adrenal adenomas . It is the most sensitive serum blood test to differentiate primary from secondary causes of hyperaldosteronism. Blood obtained when the patient has been standing for more than 2 hours are more sensitive than those from when the patient is lying down. Before the test, individuals should not restrict salt and low potassium should be corrected before

2625-536: Is an endocrine disease that results from hypocortisolism caused by adrenal gland insufficiency. Adrenal insufficiency is significant because it is correlated with decreased ability to maintain blood pressure and blood sugar, a defect that can prove to be fatal. Graves' disease involves the hyperactivity of the thyroid gland which produces the T3 and T4 hormones. Graves' disease effects range from excess sweating, fatigue, heat intolerance and high blood pressure to swelling of

2730-487: Is an indirect function of the serum potassium as probably determined by sensors in the carotid artery. Adrenocorticotropic hormone (ACTH), a pituitary peptide, also has some stimulating effect on aldosterone, probably by stimulating the formation of deoxycorticosterone , a precursor of aldosterone. Aldosterone is increased by blood loss, pregnancy, and possibly by further circumstances such as physical exertion, endotoxin shock, and burns. The aldosterone production

2835-405: Is at low. Thus, potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in "primitive" diets. Feedback by aldosterone concentration itself is of a nonmorphological character (that is, other than changes in the cells' number or structure) and is poor, so the electrolyte feedbacks predominate, short term. Hyperaldosteronism

2940-444: 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

3045-504: Is characterized by irregulated hormone release (a productive pituitary adenoma ), inappropriate response to signalling ( hypothyroidism ), lack of a gland ( diabetes mellitus type 1 , diminished erythropoiesis in chronic kidney failure ), or structural enlargement in a critical site such as the thyroid ( toxic multinodular goitre ). Hypofunction of endocrine glands can occur as a result of the loss of reserve, hyposecretion, agenesis , atrophy, or active destruction. Hyperfunction can occur as

3150-699: Is due to 21-hydroxylase deficiency. 21-hydroxylase is necessary for production of both mineralocorticoids and glucocorticoids, but not androgens . Therefore, ACTH stimulation of the adrenal cortex induces the release of excessive amounts of adrenal androgens , which can lead to the development of ambiguous genitalia and secondary sex characteristics . Adrenal tumors are commonly found as incidentalomas , unexpected asymptomatic tumors found during medical imaging . They are seen in around 3.4% of CT scans , and in most cases they are benign adenomas . Adrenal carcinomas are very rare, with an incidence of 1 case per million per year. Pheochromocytomas are tumors of

3255-400: 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. Glucocorticoids are under

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3360-435: Is nearly equal to the entire sodium content in human blood under normal glomerular filtration rates . Aldosterone, probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the dentate gyrus . Steroid receptors are intracellular since steroid hormones are able to cross the cell membrane without a specific transporter. The aldosterone mineralocorticoid receptor (MR) complex binds on

3465-477: 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. All corticosteroid hormones share cholesterol as

3570-406: Is prompted by prolactin-releasing hormone and inhibited by prolactin-inhibiting hormone . The intermediate lobe of the pituitary gland secretes only one enzyme that is melanocyte stimulating hormone . It is linked with the formation of the black pigment in our skin called melanin. The neurohypophysis stores and releases two hypothalamic hormones: The thyroid gland is located in the front of

3675-499: Is regulated by growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GHIH), or somatostatin. Hypersecretion causes gigantism in children and acromegaly in adults; hyposecretion in children causes pituitary dwarfism . Thyroid-stimulating hormone promotes normal development and activity of the thyroid gland . Thyrotropin-releasing hormone stimulates its release; negative feedback of thyroid hormone inhibits it. Adrenocorticotropic hormone stimulates

3780-423: Is regulated mainly by the renin–angiotensin–aldosterone system (RAAS), the concentration of potassium , and to a lesser extent the concentration of ACTH. Sensors of blood pressure in the juxtaglomerular apparatus of the kidneys release the enzyme renin into the blood, which starts a cascade of reactions that lead to formation of angiotensin II . Angiotensin receptors in cells of the zona glomerulosa recognize

3885-660: Is stimulated by the thyroid-stimulating hormone, secreted by the anterior pituitary. When thyroid levels are high, there is negative feedback that decreases the amount of Thyroid-stimulating hormone secreted. Most T4 is converted to T3 (a more active form) in the target tissues. Calcitonin , produced by the parafollicular cells (C cells) of the thyroid gland in response to rising blood calcium levels, depresses blood calcium levels by inhibiting bone matrix resorption and enhancing calcium deposit in bones. Excessive secretion cause hyperthyroidism and deficiency cause hypothyroidism. The parathyroid glands, of which there are 4–6, are found on

3990-466: 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

4095-460: Is the adrenal crisis , a medical emergency in which low glucocorticoid and mineralocorticoid levels result in hypovolemic shock and symptoms such as vomiting and fever. An adrenal crisis can progressively lead to stupor and coma . The management of adrenal crises includes the application of hydrocortisone injections. In secondary adrenal insufficiency, a dysfunction of the hypothalamic–pituitary–adrenal axis leads to decreased stimulation of

4200-796: 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 . 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. The adrenal medulla

4305-431: Is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland . It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure , plasma sodium (Na ), and potassium (K ) levels. It does so primarily by acting on the mineralocorticoid receptors in

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4410-406: Is the main responsible for this, and that glucocorticoids only play a role in the subsequent development of the cells. The normal function of the adrenal gland may be impaired by conditions such as infections, tumors, genetic disorders and autoimmune diseases , or as a side effect of medical therapy. These disorders affect the gland either directly (as with infections or autoimmune diseases) or as

4515-410: Is then converted to dopamine before it can be turned into noradrenaline. In the cytosol , noradrenaline is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and stored in granules. Glucocorticoids produced in the adrenal cortex stimulate the synthesis of catecholamines by increasing the levels of tyrosine hydroxylase and PNMT. Catecholamine release is stimulated by

4620-415: Is to reduce sodium and water retention but increase the retention of potassium. In other words, these drugs stimulate the excretion of sodium and water in urine, while they block the excretion of potassium. Another example is spironolactone , a potassium-sparing diuretic of the steroidal spirolactone group, which interferes with the aldosterone receptor (among others) leading to lower blood pressure by

4725-652: The adrenal cortex to release corticosteroids . Adrenocorticotropic hormone release is triggered by corticotropin -releasing hormone and inhibited by rising glucocorticoid levels. The gonadotropins — follicle-stimulating hormone and luteinizing hormone regulate the functions of the gonads in both sexes. Follicle-stimulating hormone stimulates sex cell production; luteinizing hormone stimulates gonadal hormone production. Gonadotropin levels rise in response to gonadotropin-releasing hormone . Negative feedback of gonadal hormones inhibits gonadotropin release. Prolactin promotes milk production in human females. Its secretion

4830-455: The anterior pituitary and a neural portion of the posterior pituitary , which is an extension of the hypothalamus . The hypothalamus regulates the hormonal output of the anterior pituitary and creates two hormones that it exports to the posterior pituitary for storage and later release. Four of the six anterior pituitary hormones are tropic hormones that regulate the function of other endocrine organs. Most anterior pituitary hormones exhibit

4935-612: 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. The adrenal glands are located on both sides of

5040-456: The distal tubules and collecting ducts of the nephron . It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney , thereby indirectly influencing water retention or loss, blood pressure , and blood volume . When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease . Aldosterone has exactly

5145-466: The gonads , acting in this way as a metabolic intermediate . Primarily referred to in the United States as epinephrine and norepinephrine , adrenaline and noradrenaline are catecholamines , water-soluble compounds that have a structure made of a catechol group and an amine group . The adrenal glands are responsible for most of the adrenaline that circulates in the body, but only for

5250-420: The heart ( atrial natriuretic peptide ); gastrointestinal tract organs ( gastrin , secretin , and others); the placenta (hormones of pregnancy— estrogen , progesterone , and others); the kidneys ( erythropoietin and renin ); the thymus ; skin ( cholecalciferol ); and adipose tissue ( leptin and resistin ). Endocrine glands derive from all three germ layers. The natural decrease in function of

5355-453: The mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase ). Aldosterone and corticosterone share the first part of their biosynthetic pathways. The last parts are mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase

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5460-534: The placenta for estrogen biosynthesis. Cortical development of the adrenal gland is regulated mostly by ACTH , a hormone produced by the pituitary gland that stimulates cortisol synthesis. During midgestation, the fetal zone occupies most of the cortical volume and produces 100–200 mg/day of DHEA-S , an androgen and precursor of both androgens and estrogens (female sex hormones). Adrenal hormones, especially glucocorticoids such as cortisol, are essential for prenatal development of organs, particularly for

5565-552: 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. 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: These blood vessels supply

5670-524: The thyroid , and hormones have been implicated in signaling distant tissues to proliferate, for example, the estrogen receptor has been shown to be involved in certain breast cancers . Endocrine, paracrine, and autocrine signaling have all been implicated in proliferation, one of the required steps of oncogenesis . Other common diseases that result from endocrine dysfunction include Addison's disease , Cushing's disease and Grave's disease . Cushing's disease and Addison's disease are pathologies involving

5775-434: The zona fasciculata and the zona reticularis . 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

5880-541: The DNA to specific hormone response element , which leads to gene specific transcription . Some of the transcribed genes are crucial for transepithelial sodium transport, including the three subunits of the epithelial sodium channel (ENaC), the Na /K pumps and their regulatory proteins serum and glucocorticoid-induced kinase , and channel-inducing factor , respectively. The MR is stimulated by both aldosterone and cortisol, but

5985-421: The abdomen, below and behind the stomach, is both an exocrine and an endocrine gland. The alpha and beta cells are the endocrine cells in the pancreatic islets that release insulin and glucagon and smaller amounts of other hormones into the blood. Insulin and glucagon influence blood sugar levels . Glucagon is released when the blood glucose level is low and stimulates the liver to release glucose into

6090-438: The activation of the sympathetic nervous system . Splanchnic nerves of the sympathetic nervous system innervate the medulla of the adrenal gland. When activated, it evokes the release of catecholamines from the storage granules by stimulating the opening of calcium channels in the cell membrane. The  human genome  includes approximately 20,000 protein coding genes and 70% of these  genes are expressed  in

6195-445: The adrenal cortex. Apart from suppression of the axis by glucocorticoid therapy, the most common cause of secondary adrenal insufficiency are tumors that affect the production of adrenocorticotropic hormone (ACTH) by the pituitary gland . This type of adrenal insufficiency usually does not affect the production of mineralocorticoids , which are under regulation of the renin–angiotensin system instead. Congenital adrenal hyperplasia

6300-412: The adrenal gland is derived from mesoderm , whereas the medulla is derived from the neural crest , which is of ectodermal origin. The adrenal glands in a newborn baby are much larger as a proportion of the body size than in an adult. For example, at age three months the glands are four times the size of the kidneys. The size of the glands decreases relatively after birth, mainly because of shrinkage of

6405-574: The adrenal gland. In the Western world, Addison's disease is most commonly an autoimmune condition, in which the body produces antibodies against cells of the adrenal cortex. Worldwide, the disease is more frequently caused by infection, especially from tuberculosis . A distinctive feature of Addison's disease is hyperpigmentation of the skin, which presents with other nonspecific symptoms such as fatigue. A complication seen in untreated Addison's disease and other types of primary adrenal insufficiency

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6510-456: The adrenal glands in 1563–4. However, these publications were part of the papal library and did not receive public attention, which was first received with Caspar Bartholin the Elder 's illustrations in 1611. Endocrine gland The pituitary gland hangs from the base of the brain by the pituitary stalk , and is enclosed by bone. It consists of a hormone-producing glandular portion of

6615-415: The adrenal medulla that arise from chromaffin cells . They can produce a variety of nonspecific symptoms, which include headaches, sweating, anxiety and palpitations . Common signs include hypertension and tachycardia . Surgery, especially adrenal laparoscopy , is the most common treatment for small pheochromocytomas. Bartolomeo Eustachi , an Italian anatomist, is credited with the first description of

6720-424: The back of the thyroid glands, and secrete parathyroid hormone , This causes an increase in blood calcium levels by targeting bone, the intestine, and the kidneys. The parathyroid hormone is the antagonist of calcitonin . Parathyroid hormone release is triggered by falling blood calcium levels and is inhibited by rising blood calcium levels. The adrenal glands are located above the kidneys in humans and in front of

6825-436: The baroreceptors and a negative feedback response, lowering systemic arterial pressure. Aldosterone release causes sodium and water retention, which causes increased blood volume, and a subsequent increase in blood pressure, which is sensed by the baroreceptors. To maintain normal homeostasis these receptors also detect low blood pressure or low blood volume, causing aldosterone to be released. This results in sodium retention in

6930-417: The beginning of puberty. The adrenal medulla is derived from neural crest cells , which come from the ectoderm layer of the embryo . These cells migrate from their initial position and aggregate in the vicinity of the dorsal aorta , a primitive blood vessel, which activates the differentiation of these cells through the release of proteins known as BMPs . These cells then undergo a second migration from

7035-420: The blood. Insulin increases the rate of glucose uptake and metabolism by most body cells. Somatostatin is released by delta cells and acts as an inhibitor of GH, insulin, and glucagon. The ovaries of the female, located in the pelvic cavity, release two main hormones. Secretion of estrogens by the ovarian follicles begins at puberty under the influence of follicle-stimulating hormone. Estrogens stimulate

7140-467: 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

7245-460: The body. Endocrine organs are activated to release their hormones by humoral, neural, or hormonal stimuli. Negative feedback is important in regulating hormone levels in the blood. The nervous system , acting through hypothalamic controls, can in certain cases override or modulate hormonal effects. Diseases of the endocrine glands are common, including conditions such as diabetes mellitus , thyroid disease, and obesity . Endocrine disease

7350-425: 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

7455-452: The cortex. The cortex, which almost completely disappears by age 1, develops again from age 4–5. The glands weigh about 1 gram at birth and develop to an adult weight of about 4 grams each. In a fetus the glands are first detectable after the sixth week of development. Adrenal cortex tissue is derived from the intermediate mesoderm . It first appears 33 days after fertilisation , shows steroid hormone production capabilities by

7560-477: The dorsal aorta to form the adrenal medulla and other organs of the sympathetic nervous system . Cells of the adrenal medulla are called chromaffin cells because they contain granules that stain with chromium salts, a characteristic not present in all sympathetic organs. Glucocorticoids produced in the adrenal cortex were once thought to be responsible for the differentiation of chromaffin cells. More recent research suggests that BMP-4 secreted in adrenal tissue

7665-479: The dysfunction of the adrenal gland. Dysfunction in the adrenal gland could be due to primary or secondary factors and can result in hypercortisolism or hypocortisolism. Cushing's disease is characterized by the hypersecretion of the adrenocorticotropic hormone due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. Some clinical signs of Cushing's disease include obesity, moon face, and hirsutism. Addison's disease

7770-436: The eighth week and undergoes rapid growth during the first trimester of pregnancy. The fetal adrenal cortex is different from its adult counterpart, as it is composed of two distinct zones: the inner "fetal" zone, which carries most of the hormone-producing activity, and the outer "definitive" zone, which is in a proliferative phase. The fetal zone produces large amounts of adrenal androgens (male sex hormones) that are used by

7875-570: The eyes that causes redness, puffiness and in rare cases reduced or double vision. Graves' disease is the most common cause of hyperthyroidism ; hyposecretion causes cretinism in infants and myxoedema in adults. Hyperparathyroidism results in hypercalcemia and its effects and in extreme bone wasting. Hypoparathyroidism leads to hypocalcemia , evidenced by tetany seizure and respiratory paralysis. Hyposecretion of insulin results in diabetes mellitus; cardinal signs are polyuria, polydipsia, and polyphagia. Aldosterone Aldosterone

7980-438: The female's ovaries during late middle age results in menopause . The efficiency of all endocrine glands seems to decrease gradually as ageing occurs. This leads to a generalized increase in the incidence of diabetes mellitus and a lower metabolic rate . Local chemical messengers, not generally considered part of the endocrine system, include autocrines , which act on the cells that secrete them, and paracrines , which act on

8085-464: 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 . 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

8190-432: The general population. Diseases classified as primary adrenal insufficiency (including Addison's disease and genetic causes) directly affect the adrenal cortex. If a problem that affects the hypothalamic–pituitary–adrenal axis arises outside the gland, it is a secondary adrenal insufficiency . Addison's disease refers to primary hypoadrenalism, which is a deficiency in glucocorticoid and mineralocorticoid production by

8295-418: The growth of body hair. The pineal gland is located in the diencephalon of the brain. It primarily releases melatonin , which influences daily rhythms and may have an antigonadotropic effect in humans. It may also influence the melanotropes and melanocytes located in the skin. Many body organs not normally considered endocrine organs contain isolated cell clusters that secrete hormones. Examples include

8400-431: The inner medulla , both of which produce hormones. 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

8505-445: The kidney, leading to water retention and increased blood volume. Aldosterone levels vary as an inverse function of sodium intake as sensed via osmotic pressure. The slope of the response of aldosterone to serum potassium is almost independent of sodium intake. Aldosterone is increased at low sodium intakes, but the rate of increase of plasma aldosterone as potassium rises in the serum is not much lower at high sodium intakes than it

8610-536: The kidneys in other animals. The adrenal glands produce a variety of hormones including adrenaline and the steroids aldosterone cortisol and Dehydroepiandrosterone sulfate (DHEA). Adrenaline increases blood pressure, heart rate, and metabolism in reaction to stress, the aldosterone controls the body's salt and water balance, the cortisol plays a role in stress response and the dehydroepiandrosterone sulfate (DHEA) produces aids in production of body odor and growth of body hair during puberty. The pancreas, located in

8715-410: 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 system through increased secretion of ACTH at the presence of certain molecules of the inflammatory response . Mineralocorticoid secretion

8820-436: The maturation of the lungs . The adrenal gland decreases in size after birth because of the rapid disappearance of the fetal zone, with a corresponding decrease in androgen secretion. During early childhood androgen synthesis and secretion remain low, but several years before puberty (from 6–8 years of age) changes occur in both anatomical and functional aspects of cortical androgen production that lead to increased secretion of

8925-513: The maturation of the female reproductive system and the development of secondary sexual characteristics. Progesterone is released in response to high blood levels of luteinizing hormone . It works with estrogens in establishing the menstrual cycle . The testes of the male begin to produce testosterone at puberty in response to luteinizing hormone. Testosterone promotes maturation of the male reproductive organs, development of secondary sex characteristics such as increased muscle and bone mass, and

9030-405: The mechanism described above. Aldosterone was first isolated by Sylvia Tait (Simpson) and Jim Tait in 1953; in collaboration with Tadeusz Reichstein . The corticosteroids are synthesized from cholesterol within the zona glomerulosa and zona fasciculata of adrenal cortex . Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within

9135-468: The medulla. The adrenal glands are composed of two heterogenous types of tissue. In the center is the adrenal medulla , which produces adrenaline and noradrenaline and releases them into the bloodstream, as part of the sympathetic nervous system . Surrounding the medulla is the cortex , which produces a variety of steroid hormones . These tissues come from different embryological precursors and have distinct prenatal development paths. The cortex of

9240-452: The neck, in front of the thyroid cartilage , and is shaped like a butterfly, with two wings connected by a central isthmus . Thyroid tissue consists of follicles with a stored protein called colloid, containing[thyroglobulin], a precursor to other thyroid hormones, which are manufactured within the colloid. The thyroid hormones increase the rate of cellular metabolism , and include thyroxine (T4) and triiodothyronine (T3). Secretion

9345-589: The normal adult adrenal glands. Only some 250 genes are more specifically expressed in the adrenal glands compared to other organs and tissues. The adrenal-gland-specific genes with the highest level of expression include members of the cytochrome P450 superfamily of enzymes. Corresponding proteins are expressed in the different compartments of the adrenal gland, such as CYP11A1 , HSD3B2 and FDX1 involved in steroid hormone synthesis and expressed in cortical cell layers, and PNMT and DBH involved in noradrenaline and adrenaline synthesis and expressed in

9450-476: The opposite function of the atrial natriuretic hormone secreted by the heart . Aldosterone is part of the renin–angiotensin–aldosterone system . It has a plasma half-life of less than 20 minutes. Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like lisinopril , which lowers blood pressure by blocking the angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion. The net effect of these drugs

9555-403: 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,

9660-601: The overproduction of aldosterone by the adrenal glands , when not a result of excessive renin secretion. It leads to arterial hypertension (high blood pressure) associated with hypokalemia, usually a diagnostic clue. Secondary hyperaldosteronism , on the other hand, is due to overactivity of the renin–angiotensin system . Conn's syndrome is primary hyperaldosteronism caused by an aldosterone-producing adenoma. Depending on cause and other factors, hyperaldosteronism can be treated by surgery and/or medically, such as by aldosterone antagonists . The ratio of renin to aldosterone

9765-402: The presence of another hormone. Synergism occurs when two or more hormones produce the same effects in a target cell and their results are amplified. Antagonism occurs when a hormone opposes or reverses the effect of another hormone. The endocrine glands belong to the body's control system. The hormones which they produce help to regulate the functions of cells and tissues throughout

9870-454: The production of cortisol. Causes can be further classified into ACTH -dependent or ACTH-independent. The most common cause of endogenous Cushing's syndrome is a pituitary adenoma which causes an excessive production of ACTH. The disease produces a wide variety of signs and symptoms which include obesity, diabetes, increased blood pressure, excessive body hair ( hirsutism ), osteoporosis , depression, and most distinctively, stretch marks in

9975-401: 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

10080-511: 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

10185-728: The regulation resulting from angiotensin II must take place indirectly from decreased blood flow through the liver due to constriction of capillaries. When the blood flow decreases so does the destruction of aldosterone by liver enzymes. Although sustained production of aldosterone requires persistent calcium entry through low-voltage-activated Ca channels , isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca channels entry. However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides

10290-435: The regulatory influence of the hypothalamic–pituitary–adrenal axis (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

10395-531: The skin, caused by its progressive thinning. When the zona glomerulosa produces excess aldosterone , the result is primary aldosteronism . Causes for this condition are bilateral hyperplasia (excessive tissue growth) of the glands, or aldosterone-producing adenomas (a condition called Conn's syndrome ). Primary aldosteronism produces hypertension and electrolyte imbalance, increasing potassium depletion sodium retention. Adrenal insufficiency (the deficiency of glucocorticoids ) occurs in about 5 in 10,000 in

10500-412: The steroids DHEA and DHEA-S . These changes are part of a process called adrenarche , which has only been described in humans and some other primates. Adrenarche is independent of ACTH or gonadotropins and correlates with a progressive thickening of the zona reticularis layer of the cortex. Functionally, adrenarche provides a source of androgens for the development of axillary and pubic hair before

10605-404: The substance, and upon binding they stimulate the release of aldosterone . Cells in zona reticularis of the adrenal glands produce male sex hormones, or androgens , the most important of which is DHEA . In general, these hormones do not have an overall effect in the male body, and are converted to more potent androgens such as testosterone and DHT or to estrogens (female sex hormones) in

10710-414: 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

10815-402: The test because it can suppress aldosterone secretion. An ACTH stimulation test for aldosterone can help in determining the cause of hypoaldosteronism , with a low aldosterone response indicating a primary hypoaldosteronism of the adrenals, while a large response indicating a secondary hypoaldosteronism. The most common cause of this condition (and related symptoms) is Addison's disease ; it

10920-509: 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. 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

11025-429: The vessel) is arranged in conspicuous, longitudinally oriented bundles. 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. The adrenal gland secretes

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