Editing Adrenal gland (section)

===Corticosteroids===
[[Corticosteroid]]s are a group of steroid hormones produced from the cortex of the adrenal gland, from which they are named.<ref>{{cite web|title=Corticosteroid|url=http://medical-dictionary.thefreedictionary.com/corticosteroid|website=TheFreeDictionary|access-date=23 September 2015}}</ref>
* Mineralocorticoids such as [[aldosterone]] regulate salt ("mineral") balance and blood pressure<ref name=Marieb>Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14</ref>
* Glucocorticoids such as [[cortisol]] influence metabolism rates of proteins, fats and sugars ("glucose").<ref>{{cite web|title=Corticosteroid|url=http://medical-dictionary.thefreedictionary.com/glucocorticoid|website=TheFreeDictionary|access-date=23 September 2015}}</ref>
* 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 tubule]]s and the [[Collecting duct system|collecting ducts]] by increasing the reabsorption of [[Sodium in biology|sodium]] and the excretion of both potassium and hydrogen ions.<ref name="marieb" /> Aldosterone is responsible for the reabsorption of about 2% of filtered [[glomerular filtrate]].<ref>{{cite book |author=Sherwood, Lauralee |title=Human physiology: from cells to systems |publisher=Brooks/Cole |location=Pacific Grove, CA |year=2001 |isbn=978-0-534-56826-9 |oclc= 43702042}}</ref> 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.<ref name="Kaplan.Physio"/> 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.<ref name=boron />

;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 [[Gluconeogenesis|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 [[osteoblast]]s to produce new bone tissue and decreases the absorption of calcium in the [[Human gastrointestinal tract|gastrointestinal tract]].<ref name=boron />

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.<ref name=boron /> [[Cortisone]] is an inactive product of the action of the enzyme [[11β-Hydroxysteroid dehydrogenase|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.<ref name=boron />

;Formation
[[File:Adrenal Steroids Pathways.svg|thumb|right|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 [[Steroid#Steroidogenesis|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 lipoprotein]]s (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.<ref name=williams>{{cite book|last1=Melmed|first1=S|last2=Polonsky|first2=KS|last3=Larsen|first3=PR|last4=Kronenberg|first4=HM|title=Williams Textbook of Endocrinology|date=2011|publisher=Saunders|isbn=978-1437703245|edition=12th}}</ref> In the [[lysosome]], cholesterol esters are converted to free cholesterol, which is then used for steroidogenesis or stored in the cell.<ref name="miller bose">{{cite journal|last1=Miller|first1=WL|last2=Bose|first2=HS|title=Early steps in steroidogenesis: intracellular cholesterol trafficking|journal=Journal of Lipid Research|date=2011|volume=52|issue=12|pages=2111–2135|doi=10.1194/jlr.R016675 |doi-access=free |pmid=21976778|pmc=3283258}}</ref>

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 [[mitochondrion|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.<ref name="miller bose"/>

The layers of the adrenal gland differ by function, with each layer having distinct enzymes that produce different hormones from a common precursor.<ref name=williams/> 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 [[Microsome|microsomal]] P450s and [[hydroxysteroid dehydrogenase]]s. Usually a number of intermediate steps in which pregnenolone is modified several times are required to form the functional hormones.<ref name="miller auchus">{{cite journal|last1=Miller|first1=WL|last2=Auchus|first2=RJ|title=The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.|journal=Endocrine Reviews|date=2011|volume=32|issue=1|pages=81–151|pmid=21051590|pmc=3365799|doi=10.1210/er.2010-0013}}</ref> 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.<ref name=charmandari>{{cite journal|last1=Charmandari |first1=E |last2=Brook |first2=CG |last3=Hindmarsh |first3=PC |title=Classic congenital adrenal hyperplasia and puberty. |url=http://eje-online.org/content/151/Suppl_3/U77.long |archive-url=https://archive.today/20150204104659/http://eje-online.org/content/151/Suppl_3/U77.long |url-status=dead |archive-date=2015-02-04 |journal=European Journal of Endocrinology |date=2004 |volume=151 |issue=Suppl 3 |pages=77–82 |doi=10.1530/eje.0.151U077 |pmid=15554890 |citeseerx=10.1.1.613.6853 |s2cid=27083986 }}</ref>

;Regulation
[[File:ACTH Negative Feedback.svg|thumb|right|Negative feedback in the [[hypothalamic–pituitary–adrenal axis|HPA axis]]]]
Glucocorticoids are under the regulatory influence of the [[hypothalamic–pituitary–adrenal axis|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 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]].<ref name="williams" />

Mineralocorticoid secretion is regulated mainly by the [[renin–angiotensin–aldosterone system]] (RAAS), the concentration of [[potassium]], and to a lesser extent the concentration of ACTH.<ref name="williams" /> 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 receptor]]s in cells of the zona glomerulosa recognize the substance, and upon binding they stimulate the release of [[aldosterone]].<ref name=crowley>{{cite journal|last1=Crowley|first1=SD|last2=Coffman|first2=TM|title=Recent advances involving the renin–angiotensin system|journal=Experimental Cell Research|date=2012|volume=318|issue=9|pages=1049–1056|doi=10.1016/j.yexcr.2012.02.023|pmid=22410251|pmc=3625040}}</ref>