Adrenal cortex Corticosteroids

The tenn corticosteroids refers to steroid hormones secreted by the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. 

Adrenocorticotropic hormone derives from the anterior pituitary in response to the leptin-or stress-induced anorexigenic, hypothalamic CRH. Corticotropin (like enkephalins and MSHs) derives from a precursor polypeptide pro-opiomelanocortin. Corticotropin induces the catabolic adrenal cortex corticosteroid cortisol and the mineralocorticoid aldosterone (Chapter 11) and is an important regulator of immune responses including chemotaxis and phagocytosis. Corticotropin acts via GPCRs to activate Gas and increase cAMP in anterior pituitary cells. 

Cosyntropin ACTH analog, stimulates adrenal cortex Corticosteroid substitute diagnosis infantile spasms (seizures) Cosyntropin is a 1-24 amino acid active fragment of ACTH... 

Progesterone, cortisol, cortisone, aldosterone and related compounds have hormone activity in animals (E 3.1). Progesterone regulates the metabolic activity of the gonads. It is synthesized mainly in the corpus luteum and the placenta. Cortisol, cortisone, and aldosterone influence carbohydrate and mineral metabolism. They are formed in the adrenal cortex (corticosteroids), but also in the gonads and the placenta. All compounds mentioned are used in medicine (F 2) and are produced by the pharmaceutical industry, e.g., from steroid saponins (D 6.4.2) or steroid alkaloids (D 6.4.3). 

The next step in increasing complexity of structure is the hormone of pregnancy, progesterone (5), and the hormones of the adrenal cortex, corticosteroids, as an example of which cortisone (6) may be mentioned. 

Control of secretion of anterior pituitary hormones also includes inhibition by hormones produced by target organs. For example, CRH stimulates the anterior pituitary to secrete ACTH, which in turn stimulates the adrenal cortex to secrete corticosteroids. Corticosteroids then feed back to inhibit the secretion of ACTH. Feedback mechanisms are important for the control of most hormones. For example, insulin (qv) secretion from the pancreas increases in response to increased blood glucose resulting from ingestion of a meal. Insulin increases tissue uptake and metaboHsm of glucose, which lowers blood glucose and in turn reduces insulin secretion. 

CRH (Corticotropin releasing hormone) is expressed in the nucleus paraventricularis of the hypothalamus and drives the stress hormone system by activating synthesis and release of corticotropin at the pituitary and in turn corticosteroid from the adrenal cortex. CRH is also expressed at many other brain locations not involved in neuroendocrine regulation, e.g. the prefrontal cortex and the amygdala. Preclinical studies have shown that CRH also coordinates the behavioral adaptation to stress (e.g. anxiety, loss of appetite, decreased sleepiness, autonomic changes, loss of libido). 

Corticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystalline steroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available The potent antiinflammatory action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders. The corticosteroids are discussed in Chapter 50. 

This section of the chapter discusses FSH, LH, GH, and ACTH. FSH and LH are called gonadotropins because they influence the gonads (the organs of reproduction). GH, also called somatotropin, contributes to the growth of the body during childhood, especially the growth of muscles and bones. ACTH is produced by the anterior pituitary and stimulates the adrenal cortex to secrete the corticosteroids. The anterior pituitary hormone, TSH, is discussed in Chapter 51. Prolactin, which is also secreted by the anterior pituitary, stimulates the production of breast milk in the postpartum patient Additional functions of prolactin are not well understood. Prolactin is the only anterior pituitary hormone that is not used medically. 

This section of the chapter discusses the hormones produced by the adrenal cortex or the adrenocortical hormones, which are the glucocorticoids and mineralocorticoids. These hormones are essential to life and influence many organs and structures of the body. The glucocorticoids and mineralocorticoids are collectively called corticosteroids. 

The interaction between the adrenal cortex of the foetus and the placenta in production of steroid hormones is complex. In outline, the placenta produces progesterone from cholesterol (which is available from the maternal blood) whereas the foetal adrenal cortex produces corticosteroids and androgens from the progesterone produced in the placenta. The placenta then converts some of these androgens into oestrogens. The interplay between the placenta and the foetal adrenal cortex is acknowledged by the use of the term foeto-placental unit to describe steroido-... 

The maximal activity of the adrenal cortex is between 2 and 8 am, and it is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocortical activity the least when given at the time of maximal activity (am). Therefore, administer glucocorticoids in the morning prior to 9 am. 

Corticosteroids Adrenal insufficiency, antiinflammatory agents, immunosuppressants Adrenal cortex... 

Glucocorticoids and mineralocorticoids are uniquely produced by the adrenal cortex, and are collectively termed corticosteroids. Apart from aldosterone, glucocorticoid secretion is regulated by the pituitary hormone, corticotrophin. The principal corticosteroids synthesized in the body are illustrated in Figure 1.6. Glucocorticoids generally exhibit weak mineralocorticoid actions and vice versa. 

Figure 1.6. Corticosteroids produced naturally in the adrenal cortex...

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

Cortisone is a natural corticosteroid secreted by the adrenal cortex along with many steroidal hormones. It has mainly glucocorticoidal activity and some degree of mineralo-corticoid activity. 

It is a polypeptide of 39 amino acid residues of molecular weight approximately 4,500. It is secreted by basophil cells under the control of CRF (corticotropin releasing factor) from the hypothalamus. ACTH controls the growth of adrenal cortex and the synthesis of corticosteroids and is essential to life. The action of ACTH on adrenal cortex is mediated through cyclic AMP. 

Corticosteroids are synthesized in the adrenal cortex under the influence of ACTH. Glucocorticoids affect the metabolism of carbohydrates, proteins, fats, calcium and electrolytes. 

Biosynthesis in anterior pituitary, stimulation of formation of corticosteroids in adrenal cortex, release of fatty acids from adipose tissue,... 

Transient elevations in blood pressure and heart rate occur with seizures, probably as a result of increased sympathetic stimulation that leads to increases in norepinephrine levels. Hypertension or increased pretreatment heart rate are strongly predictive of peak postictal change in both heart rate and blood pressure ( 38). Increased parasympathetic stimulation decreases the heart rate as a result of inhibition of the sinoatrial node. Stimulation of the adrenal cortex leads to increased plasma corticosteroids and stimulation of the adrenal medulla, which may also contribute to increases in blood pressure and heart rate. 

The natural adrenocortical hormones are steroid molecules produced and released by the adrenal cortex. Both natural and synthetic corticosteroids are used for the diagnosis and treatment of disorders of adrenal function. They are also used—more often and in much larger doses—for treatment of a variety of inflammatory and immunologic disorders. 

Steroid hormones are secreted on demand from their tissues of origin in response to hormonal signals. The corticosteroids and androgens are made in different regions of the adrenal cortex, and are secreted into blood in response to different signals. 

Corticotropin (corticotrophin adrenocorticotrophin ACTH) is a straight-chain polypeptide with39 amino acid residues, and its function is to control the activity of the adrenal cortex, particularly the production of corticosteroids. Secretion of the hormone is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH was formerly used as an alternative to corticosteroid therapy in rheumatoid arthritis, but its value was limited by variable therapeutic response. ACTH may be used to test adrenocortical function. It has mainly been replaced for this purpose by the synthetic analoguetetracosactide (tetracosactrin) (Figure 7.10), which contains the first 24 amino acid residues of ACTH, and is preferred because of its shorter duration of action and lower allergenicity. 

The adrenal cortex synthesizes corticosteroids (glucocorticoids and mineralocor-ticoids), which differ in activities. In humans, cortisol is the main glucocorticoid, and aldosterone is a main mineralocorticoid. Steroid therapy causes severe potential side effects, hence a careful consideration is always exercised before starting therapy. These are used in variety of disorders such as rheumatic disorder, renal disease, allergic manifestation, bronchial asthma, skin diseases, infectious diseases, malignancy, and hepatic diseases. 

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