Adrenal cortex adrenocorticotropic hormone

Pregnenolone is transported from the mitochondria to the ER, where a hydroxyl oxidation and migration of the double bond yield progesterone. Pregnenolone synthesis in the adrenal cortex is activated by adrenocorticotropic hormone (ACTH), a peptide of 39 amino acid residues secreted by the anterior pituitary gland. 

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

A trophic hormone acts on another endocrine gland to stimulate secretion of its hormone. For example, thyrotropin, or thyroid-stimulating hormone (TSH), stimulates the secretion of thyroid hormones. Adrenocorticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete the hormone cortisol. Both trophic hormones are produced by the pituitary gland in fact, many trophic hormones are secreted by the pituitary. The pituitary gland is sometimes referred to as the "master gland" because its hormones regulate the activity of other endocrine glands. 

Corticotropin (adrenocorticotropic hormone, ACTH) regulates the function of the adrenal cortex and has numerous other effects on metabolism. It contains 39 amino acids in the form of a random coil, owing to the presence of several proline residues that prevent helix formation. Species differences are seen in amino acids 25-39 the rest of the ACTH molecule is identical in all animals and humans. The first 24 amino acids are responsible for all of the biological action of ACTH synthetic human ACTHj 24 is known as cosyntropin. 

The primary glucocorticoid released in humans is cortisol (also known as hydrocortisone). Cortisol synthesis and secretion are under the control of specific hypothalamic and pituitary hormones.7,24 31 Corticotropinreleasing hormone (CRH) from the hypothalamus stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH travels in the systemic circulation to reach the adrenal cortex, where it stimulates cortisol synthesis. Cortisol then travels in the bloodstream to various target tissues to exert a number of physiologic effects (see Physiologic Effects of Glucocorticoids, later). 

Much of this older work must be re-evaluated on the basis of availability of glycogen. A relationship to the adrenal-cortex secretion might be uncovered, but this is a possibility not yet explored. In man, the injection of adrenocorticotropic hormone (ACTH) has been reported not to influence the excretion of (endogenous) glucuronic acid or of hexosamine.176... 

The adrenal glands are located anatomically above the kidneys. They comprise a three-layer cortex and a medulla. The medulla is the source of catecholamines such as epinephrine, the fight-or-flight hormone. The cortex is the source of aldosterone, the primary mineralocorticoid that is involved in the regulation of sodium reabsorption in the kidneys. In addition, the cortex is also the source of steroids known as glucocorticoids, of which cortisol is the principal endogenous representative. Synthesis and release of cortisol is under the control of adrenocorticotropic hormone (ACTH). 

Adrenocorticotropic hormone (Fig. 4) stimulates the cells of the adrenal cortex into the secretion and production of steroid hormones. Conversely, the pituitary secretion of ACTH is inhibited by the adrenal hormones via a feedback mechanism. 

Adrenocorticotropic hormone (ACTH) Polypeptide with 39 amino acids Corticotropin-releasing hormone (CRH) peptide with 41 amino acids Unknown Causes release of steroid hormones from adrenal cortex... 

ACTH (adrenocorticotropic hormone, corticotropin) is a 39-amino-acid peptide synthesized and secreted by the corticotrope cells of the anterior lobe of the pituitary gland. ACTH acts on several target tissues, including the adrenal cortex, adipose tissue and brain. It is synthesized as part of proopiomelanocortin (POMC) as amino acids 132-170 of this molecule, which is proteolytically cleaved to produce ACTH [1],... 

The glucocorticoid cortisol is secreted from the adrenal cortex as a stress response under the control of adrenocorticotropic hormone (ACTH, corticotropin) produced by the anterior pituitary. Cortisol promotes catabolism by inducing synthesis of specific proteins. Cortisol binds to a cytosolic cortisol receptor which then translocates to the nucleus and switches on the expression of specific genes, notably that for PEP carboxykinase (PEPCK). Cortisol-induced expression of the key gluconeogenesis enzyme PEPCK increases levels of the enzyme and hence increases gluconeogenesis and available blood glucose. The cAMP-and cortisol-mediated pathways for induction of PEPCK expression are further linked by CREB-dependent expression of a coactivator protein PGC-1 that promotes cortisol-dependent expression of PEPCK. 

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. 

Melanocortins. This is a generic name for the peptide hormones, melanotropin and corticotropin, (ACTH, adrenocorticotropic hormone), because both hormones are formed in the anterior pituitary gland from the same melanocortin precursor. Melanotropin controls melanocyte growth and pigmentation. Corticotropin stimulates the production of glucocorticoids and mineralocorticoids, such as aldosteron, in the adrenal cortex. The Melanocortin-pathway is somehow involved in the control of appetite and body weight. 

It is also believed that vitamin C is involved in the process of steroidogenesis since the adrenal cortex contains high levels of vitamin C, which are depleted upon adrenocorticotropic hormone (ACTH) stimulation of the gland. 

Cortisol. Cortisol, secreted by the adrenal cortex in response to adrenocorticotropic hormone (ACTH), stimulates gluconeogenesis and increases the breakdown of protein and fat. Patients with Cushing s syndrome have increased cortisol owing to a tumor or hyperplasia of the adrenal cortex and may become hyperglycemic. In contrast, people with Addisons disease have adrenocortical insufficiency because of destruction or atrophy of the adrenal cortex and may exhibit hypoglycemia. ... 

Corticotropin is a peptide hormone secreted by the adenohypophysis, one of the derivatives of pro-opiomelanocortin (POMC) it acts primarily on the adrenal cortex, stimulating its grovrth and the secretion of corticosteroids. Its production is increased during times of stress. It is also known as adrenocorticotropic hormone, ACTH, corticotrophin, adrenocorticotrophin, and adrenocorticotropin. 

Adrenocorticotropic Hormone (ACTH) (Corticotropin) Anterior Pituitary (Corticotroph) 39 aa 2p25 Stimulates steroidogenesis in all three zones of the adrenal cortex, thereby increasing secretion of cortisol, DHEAS, and aldosterone. Stimulated by CRH and inhibited by cortisol. 

Hench, P. S., Kendall, E. C., Slocumb, C. H Policy, H. F. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticos-terone compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc. Mayo Clin. 1949, 24, 181-197. 

The use of corticosteroids in the treatment of septic shock has been a topic of controversy for many years. A meta-analysis of early studies of steroids in sepsis demonstrated a lack of benefit and potential harm in sepsis and septic shock. There is a renewed interest in corticosteroid use because of the increased awareness of adrenocortical insufficiency in critically ill patients with septic shock. Relative adrenal insufficiency has been defined as a poor adrenal response [<250 nmol/L (9 mcg/dL) irrespective of the initial serum cortisol level] to a dose of synthetic adrenocorticotropic hormone (ACTH), indicating a low fnnctional reserve of the adrenal cortex. Although absolute insufficiency is rare, relative adrenocortical insufficiency in the presence of normal or high cortisol concentrations at baseline is present in 30% to 50% of patients with septic shock and is associated with a poor outcome. ... 

Glucocorticoid secretion from the adrenal cortex is stimulated by corticotropin or adrenocorticotropic hormone (ACTH) that is released from the anterior pituitary in response to hypothalamic-mediated release of corticotropinreleasing hormone (CRH). 

ACTH Adrenocorticotropin, adrenocorticotropic hormone a polypeptide hormone released from the anterior pituitary into the bloodstream in response to the binding of CRH. ACTH binds to receptors in the adrenal cortex, causing the synthesis and release of cortisol. 

---