View source for Steroid hormone

{{short description|Substance with biological function}}
{{Infobox drug class
| Image = Estradiol.svg
| ImageClass = skin-invert-image
| Alt = 
| Caption = [[Estradiol]], an important [[estrogen]] steroid hormone in both women and men.
| Width = 225px
| Synonyms = Adrenal steroid; Gonadal steroid
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| Use = Various
| ATC_prefix = 
| Biological_target = [[Steroid hormone receptor]]s
| Chemical_class = [[Steroid]]al; [[Nonsteroidal]]
<!-- Clinical data -->
| Drugs.com = 
| Consumer_Reports = 
| medicinenet = 
| rxlist = 
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| MeshID = 
}}

A '''steroid hormone''' is a [[steroid]] that acts as a [[hormone]]. Steroid hormones can be grouped into two classes: [[corticosteroid]]s (typically made in the [[adrenal cortex]], hence ''cortico-'') and [[sex steroid]]s (typically made in the [[gonad]]s or [[placenta]]). Within those two classes are five types according to the [[receptor (biochemistry)|receptor]]s to which they bind: [[glucocorticoid]]s and [[mineralocorticoid]]s (both corticosteroids) and [[androgen]]s, [[estrogen]]s, and [[progestogen]]s (sex steroids).<ref>{{Cite web|title=Steroid hormones - Latest research and news {{!}} Nature|url=https://www.nature.com/subjects/steroid-hormones|access-date=2021-12-06|website=www.nature.com|language=en}}</ref><ref>{{Cite web|title=steroid hormone {{!}} Definition, Classification, & Function {{!}} Britannica|url=https://www.britannica.com/science/steroid-hormone|access-date=2021-12-06|website=www.britannica.com|language=en}}</ref> [[Vitamin D]] derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as [[ligand (biochemistry)|receptor ligands]].

Steroid hormones help control [[metabolism]], [[inflammation]], [[immunity (medical)|immune functions]], [[osmoregulation|salt and water balance]], development of [[Secondary sex characteristic|sexual characteristics]], and the ability to withstand injury and illness. The term '''steroid''' describes both hormones produced by the body and artificially produced medications that duplicate the action for the naturally occurring steroids.<ref>{{cite journal|vauthors=Funder JW, Krozowski Z, Myles K, Sato A, Sheppard KE, Young M |title= Mineralocorticoid receptors, salt, and hypertension |year = 1997| journal= Recent Prog Horm Res | volume= 52  |pages = 247–260 |pmid= 9238855  }}</ref><ref name=gup>{{cite journal|vauthors=((Gupta BBP)), Lalchhandama K |title= Molecular mechanisms of glucocorticoid action |year = 2002|url=http://www.currentscience.ac.in/Downloads/article_id_083_09_1103_1111_0.pdf | journal= Current Science | volume= 83 | issue= 9 |pages = 1103–1111 }}</ref><ref>{{cite journal| author= Frye CA |title= Steroids, reproductive endocrine function, and affect. A review |year = 2009| journal= Minerva Ginecol | volume= 61 | issue= 6 |pages = 541–562 |pmid= 19942840 }}</ref>

==Synthesis==
{{Further information|Steroidogenesis}}

[[File:Steroidogenesis.svg|thumb|400px|class=skin-invert-image|[[Steroidogenesis]] with enzymes and intermediates.<ref name="HäggströmRichfield2014">{{cite journal|last2=Richfield|first2=David|year=2014|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005|issn=2002-4436|last1=Häggström|first1=Mikael|doi-access=free}}</ref>]]
The natural steroid hormones are generally synthesized from [[cholesterol]] in the [[gonad]]s and [[adrenal gland]]s. These forms of hormones are [[lipid]]s. They can pass through the cell membrane as they are fat-soluble,<ref name="HeffnerSchust2010">{{cite book|author1=Linda J. Heffner|author2=Danny J. Schust|title=The Reproductive System at a Glance|url=https://archive.org/details/reproductivesyst03edheff|url-access=registration|access-date=28 November 2010|year=2010|publisher=John Wiley and Sons|isbn=978-1-4051-9452-5|pages=[https://archive.org/details/reproductivesyst03edheff/page/16 16]–}}</ref> and then bind to [[steroid hormone receptor]]s (which may be nuclear or cytosolic depending on the steroid hormone) to bring about changes within the cell. Steroid hormones are generally carried in the blood, bound to specific carrier [[protein]]s such as [[sex hormone-binding globulin]] or [[corticosteroid-binding globulin]]. Further conversions and catabolism occurs in the liver, in other "peripheral" tissues, and in the target tissues.

{{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}}

===Synthetic steroids and sterols===
A variety of synthetic steroids and sterols have also been contrived. Most are steroids, but some [[nonsteroidal]] molecules can interact with the steroid receptors because of a similarity of shape. Some synthetic steroids are weaker or stronger than the natural steroids whose receptors they activate.<ref>{{cite journal|vauthors=Nahar L, Sarker SD, Turner AB |title= A review on synthetic and natural steroid dimers: 1997-2006 |year = 2007| journal= Curr Med Chem | volume=  14| issue= 12 |pages = 1349–1370 |pmid= 17504217 |doi=10.2174/092986707780597880}}</ref>

Some examples of synthetic steroid hormones:

* [[Glucocorticoid]]s: [[alclometasone]], [[prednisone]], [[dexamethasone]], [[triamcinolone]], [[cortisone]]
* [[Mineralocorticoid]]: [[fludrocortisone]]
* Vitamin D: [[dihydrotachysterol]]
* Androgens: [[oxandrolone]], [[oxabolone]], [[nandrolone]] (also known as anabolic-androgenic steroids or simply [[anabolic steroid]]s)
* Oestrogens: [[diethylstilbestrol]] (DES) and [[Ethinylestradiol|ethinyl estradiol]] (EE)
* Progestins: [[norethisterone]], [[medroxyprogesterone acetate]], [[hydroxyprogesterone caproate]].

Some steroid antagonists:

* Androgen: [[cyproterone acetate]]
* Progestins: [[mifepristone]], [[gestrinone]]

==Transport==
[[File:Free Hormone Hypothesis 2.jpg|thumb|class=skin-invert-image|Free hormone hypothesis 2]]
Steroid hormones are transported through the blood by being bound to carrier proteins—serum proteins that bind them and increase the hormones' solubility in water. Some examples are [[sex hormone-binding globulin]] (SHBG), [[corticosteroid-binding globulin]], and [[albumin]].<ref>{{cite journal | vauthors = Adams JS | year = 2005 | title = "Bound" to work: The free hormone hypothesis revisited | journal = Cell | volume = 122 | issue = 5| pages = 647–9 | doi=10.1016/j.cell.2005.08.024| pmid = 16143095 | doi-access = free }}</ref> Most studies say that hormones can only affect cells when they are not bound by serum proteins. In order to be active, steroid hormones must free themselves from their blood-solubilizing proteins and either bind to extracellular receptors, or passively cross the cell membrane and bind to [[nuclear receptors]]. This idea is known as the free hormone hypothesis. This idea is shown in Figure 1 to the right.
[[File:Endocytosis of Steroid Hormones.jpg|thumb|class=skin-invert-image|This shows a possible pathway through which steroid hormones are endocytosed and proceed to affect cells via a genomic pathway.]]
One study has found that these steroid-carrier complexes are bound by [[LRP2|megalin]], a membrane receptor, and are then taken into cells via [[endocytosis]]. One possible pathway is that once inside the cell these complexes are taken to the lysosome, where the carrier protein is degraded and the steroid hormone is released into the cytoplasm of the target cell. The hormone then follows a genomic pathway of action. This process is shown in Figure 2 to the right.<ref>{{cite journal | vauthors = Hammes A | year = 2005 | title = Role of endocytosis in cellular uptake of sex steroids | journal = Cell | volume = 122 | issue = 5| pages = 751–62 | doi=10.1016/j.cell.2005.06.032| pmid = 16143106 | doi-access = free }}</ref> The role of endocytosis in steroid hormone transport is not well understood and is under further investigation.

In order for steroid hormones to cross the [[lipid bilayer]] of cells, they must overcome energetic barriers that would prevent their entering or exiting the membrane. [[Gibbs free energy]] is an important concept here. These hormones, which are all derived from cholesterol, have hydrophilic functional groups at either end and hydrophobic carbon backbones. When steroid hormones are entering membranes free energy barriers exist when the functional groups are entering the hydrophobic interior of membrane, but it is energetically favorable for the hydrophobic core of these hormones to enter lipid bilayers. These energy barriers and wells are reversed for hormones exiting membranes. Steroid hormones easily enter and exit the membrane at physiologic conditions. They have been shown experimentally to cross membranes near a rate of 20 μm/s, depending on the hormone.<ref name=Oren2004>{{cite journal | vauthors = Oren I | year = 2004 | title = Free diffusion of steroid hormones across biomembranes: A simplex search with implicit solvent model calculations | journal = Biophysical Journal | volume = 87 | issue = 2| pages = 768–79 | doi=10.1529/biophysj.103.035527| pmid = 15298886 | pmc = 1304487 | bibcode = 2004BpJ....87..768O }}</ref>

Though it is energetically more favorable for hormones to be in the membrane than in the ECF or ICF, they do in fact leave the membrane once they have entered it. This is an important consideration because cholesterol—the precursor to all steroid hormones—does not leave the membrane once it has embedded itself inside. The difference between cholesterol and these hormones is that cholesterol is in a much larger negative Gibb's free energy well once inside the membrane, as compared to these hormones. This is because the aliphatic tail on cholesterol has a very favorable interaction with the interior of lipid bilayers.<ref name=Oren2004/>

==Mechanisms of action and effects==

There are many different mechanisms through which steroid hormones affect their target cells. All of these different pathways can be classified as having either a genomic effect or a non-genomic effect. Genomic pathways are slow and result in altering transcription levels of certain proteins in the cell; non-genomic pathways are much faster.
[[File:1803 Binding of Lipid-Soluble Hormones.jpg|thumb|class=skin-invert-image|Flowchart showing the binding of a steroid hormone to a target cell]]

===Genomic pathways===

The first identified mechanisms of steroid hormone action were the genomic effects.<ref name=Rousseau2013>{{cite journal | vauthors = Rousseau G | year = 2013 | title = Fifty years ago: The quest for steroid hormone receptors | journal = Molecular and Cellular Endocrinology | volume = 375 | issue = 1–2| pages = 10–3 | doi=10.1016/j.mce.2013.05.005 | pmid=23684885| s2cid = 24346074 }}</ref> In this pathway, the free hormones first pass through the cell membrane because they are fat soluble.<ref name="HeffnerSchust2010"/> In the cytoplasm, the steroid may or may not undergo an [[enzyme]]-mediated alteration such as reduction, hydroxylation, or aromatization. Then the steroid binds to a specific [[steroid hormone receptor]], also known as a [[nuclear receptor]], which is a large metalloprotein.  Upon steroid binding, many kinds of steroid receptors [[protein dimer|dimer]]ize: two receptor subunits join together to form one functional [[DNA]]-binding unit that can enter the cell nucleus. Once in the nucleus, the steroid-receptor ligand complex binds to specific [[DNA]] sequences and induces transcription of its target [[gene]]s.<ref name=gup/><ref>{{cite journal|vauthors=Moore FL, Evans SJ |title= Steroid hormones use non-genomic mechanisms to control brain functions and behaviors: a review of evidence |year = 1995| journal= Brain Behav Evol | volume=  54| issue= 4 |pages = 41–50 |pmid= 10516403 |doi= 10.1159/000006610 |s2cid= 1998076 }}</ref><ref>{{cite journal|vauthors=Marcinkowska E, Wiedłocha A |title=Steroid signal transduction activated at the cell membrane: from plants to animals  |year = 2002| journal= Acta Biochim Pol | volume=  49| issue= 9 |pages = 735–745 |doi=10.18388/abp.2002_3782 |pmid= 12422243 |doi-access= free }}</ref><ref name=Rousseau2013/>

===Non-genomic pathways===
Because non-genomic pathways include any mechanism that is not a genomic effect, there are various non-genomic pathways. However, all of these pathways are mediated by some type of [[steroid hormone receptor]] found at the plasma membrane.<ref>{{cite journal | vauthors = Wang C, Liu Y, Cao JM | year = 2014 | title = G protein-coupled receptors: Extranuclear mediators for the non-genomic actions of steroids | journal = International Journal of Molecular Sciences | volume = 15 | issue = 9| pages = 15412–25 | doi=10.3390/ijms150915412 | pmid=25257522 | pmc=4200746| doi-access = free }}</ref> Ion channels, transporters, [[G-protein coupled receptor]]s (GPCR), and membrane fluidity have all been shown to be affected by steroid hormones.<ref name=Oren2004/> Of these, GPCR linked proteins are the most common. For more information on these proteins and pathways, visit the [[steroid hormone receptor]] page.

==See also==
* [[List of investigational sex-hormonal agents]]
* [[Membrane steroid receptor]]

==References==
{{Reflist|2}}

==Further reading==
*{{cite journal | pmid = 10592444 | volume=51 Suppl 3 | issue=3 | title=Mechanism of puberty | year=1999 | journal=Horm. Res. | pages=52–4 | vauthors=Brook CG | doi=10.1159/000053162| s2cid=33671883 }}
*{{cite journal | pmid = 8742125 | volume=45 | issue=1–2 | title=Role of growth hormone and sex steroids in achieving and maintaining normal bone mass | year=1996 | journal=Horm. Res. | pages=86–93 | vauthors=Holmes SJ, Shalet SM | doi=10.1159/000184765}}
* {{cite journal | vauthors = Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, Forabosco A, Schlessinger D | date = Jan 2007 | title = Determination and stability of sex | journal = BioEssays | volume = 29 | issue = 1| pages = 15–25 | doi = 10.1002/bies.20515 | pmid = 17187356 | s2cid = 23824870 }}
*{{cite journal | pmid = 9660168 | volume=76 | issue=7 | title=Exploring the role of sex steroids through studies of receptor deficient mice | date=June 1998 | journal=J. Mol. Med. | pages=497–511 | vauthors=Couse JF, Korach KS | doi=10.1007/s001090050244| s2cid=6470903 | url=https://zenodo.org/record/1232579 }}
*{{cite journal | pmid = 1330863 | volume=37 Suppl 3 | issue=3 | title=Steroid hormones: effect on brain development and function | year=1992 | journal=Horm. Res. | pages=1–10 | vauthors=McEwen BS | doi=10.1159/000182393}}
* {{cite journal | vauthors = Simons  | date = Aug 2008 | title = physiological versus pharmacological steroid hormone actions | journal = BioEssays | volume = 30 | issue = 8| pages = 744–56 | doi = 10.1002/bies.20792 | pmid = 18623071 | pmc=2742386}}
* {{cite journal|last=Han|first=Thang S.|author2=Walker, Brian R. |author3=Arlt, Wiebke |author4= Ross, Richard J. |title=Treatment and health outcomes in adults with congenital adrenal hyperplasia|journal=Nature Reviews Endocrinology|date=17 December 2013|volume=10|issue=2|pages=115–124|doi=10.1038/nrendo.2013.239|pmid=24342885| s2cid=6090764 |postscript=Figure 2: The adrenal steroidogenesis pathway.}}

==External links==
* [https://web.archive.org/web/20090407060724/http://www.nursa.org/template.cfm?threadId=11320 An animated and narrated tutorial about nuclear receptor signaling]
*[https://web.archive.org/web/20111023232815/http://www.elmhurst.edu/~chm/vchembook/556steroids.html Virtual Chembook]
*[https://archive.today/20121217023647/http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Steroids/Steroids.HTML stedwards.edu]
*[http://biology.about.com/od/cellularprocesses/a/aa073004a.htm How Steroid Hormones Work]

{{Hormones}}
{{Steroid hormones}}
{{Receptor/signaling modulators}}
{{Authority control}}

{{DEFAULTSORT:Steroid Hormone}}

[[Category:Steroid hormones| ]]
[[Category:Steroids]]