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A '''prohormone''' is a committed [[Precursor (chemistry)|precursor]] of a [[hormone]] consisting of [[Peptide hormone|peptide hormones]] synthesized together, having a minimal hormonal effect by itself because of its expression-suppressing structure.<ref name=":7" /> Prohormones can travel the [[blood stream]] as a hormone in an inactivated form, ready to be activated later in the cell by [[post-translational modification]].<ref name=":7">{{Citation|last=Friedman|first=Theodore C.|title=Prohormones|date=2004-01-01|url=https://www.sciencedirect.com/science/article/pii/B012475570401074X|work=Encyclopedia of Endocrine Diseases|pages=91–98|editor-last=Martini|editor-first=Luciano|place=New York|publisher=Elsevier|language=en|doi=10.1016/b0-12-475570-4/01074-x|isbn=978-0-12-475570-3|access-date=2021-12-04|last2=Cool|first2=David R.}}</ref><ref name=":0">{{Cite book|last=Miller|first=Benjamin Frank |title=Miller-Keane Encyclopedia & dictionary of medicine, nursing & allied health|date=1997|publisher=Saunders|author2=Claire Brackman Keane|isbn=0-7216-6278-1|edition=6th|location=Philadelphia|oclc=36465055}}</ref> |
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The body naturally produces prohormones as a way to regulate hormone expression, making them an optimal storage and transportation unit for inactive hormones. Once prohormones are needed to be expressed, [[prohormone convertase]], a protein, cleaves the prohormones and separates them into one or more active hormones.<ref name=":1">{{Citation|last=Dhanvantari|first=Savita|title=Prohormone Convertases|date=2004-01-01|url=https://www.sciencedirect.com/science/article/pii/B012475570401091X|work=Encyclopedia of Endocrine Diseases|pages=84–90|editor-last=Martini|editor-first=Luciano|place=New York|publisher=Elsevier|language=en|isbn=978-0-12-475570-3|access-date=2021-12-09|last2=Cawley|first2=Niamh X.|last3=Loh|first3=Y. Peng}}</ref> Often in nature, this cleaving process happens immediately, and a prohormone is quickly converted to a set of peptide hormones.<ref name=":5">{{Citation|last=Alarcon|first=Cristina|title=Insulin Processing|date=2003-01-01|url=https://www.sciencedirect.com/science/article/pii/B0123411033001753|work=Encyclopedia of Hormones|pages=359–368|editor-last=Henry|editor-first=Helen L.|place=New York|publisher=Academic Press|language=en|doi=10.1016/b0-12-341103-3/00175-3|isbn=978-0-12-341103-7|access-date=2021-12-09|last2=Wicksteed|first2=Barton|last3=Rhodes|first3=Christopher J.|editor2-last=Norman|editor2-first=Anthony W.}}</ref> |
The body naturally produces prohormones as a way to regulate hormone expression, making them an optimal storage and transportation unit for inactive hormones. Once prohormones are needed to be expressed, [[prohormone convertase]], a protein, cleaves the prohormones and separates them into one or more active hormones.<ref name=":1">{{Citation|last=Dhanvantari|first=Savita|title=Prohormone Convertases|date=2004-01-01|url=https://www.sciencedirect.com/science/article/pii/B012475570401091X|work=Encyclopedia of Endocrine Diseases|pages=84–90|editor-last=Martini|editor-first=Luciano|place=New York|publisher=Elsevier|language=en|isbn=978-0-12-475570-3|access-date=2021-12-09|last2=Cawley|first2=Niamh X.|last3=Loh|first3=Y. Peng}}</ref> Often in nature, this cleaving process happens immediately, and a prohormone is quickly converted to a set of one or more peptide hormones.<ref name=":5">{{Citation|last=Alarcon|first=Cristina|title=Insulin Processing|date=2003-01-01|url=https://www.sciencedirect.com/science/article/pii/B0123411033001753|work=Encyclopedia of Hormones|pages=359–368|editor-last=Henry|editor-first=Helen L.|place=New York|publisher=Academic Press|language=en|doi=10.1016/b0-12-341103-3/00175-3|isbn=978-0-12-341103-7|access-date=2021-12-09|last2=Wicksteed|first2=Barton|last3=Rhodes|first3=Christopher J.|editor2-last=Norman|editor2-first=Anthony W.}}</ref> |
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| ⚫ | Examples of natural, human prohormones include [[proinsulin]] and [[pro-opiomelanocortin]], but the most widespread prohormones in use are synthetic and labeled as anabolic steroid precursors, used as [[Performance-enhancing substance|ergogenic]] or [[Anabolic steroid|anabolic agents]] for muscle growth.<ref name=":2">{{Cite journal|last=Powers|first=Michael E.|date=2002|title=The Safety and Efficacy of Anabolic Steroid Precursors: What is the Scientific Evidence?|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC164360/|journal=Journal of Athletic Training|volume=37|issue=3|pages=300–305|issn=1062-6050|pmid=16558675}}</ref> A commonly consumed example of said precursors are [[androstenedione]] and [[androstenediol]], both of which are currently [[Drug Enforcement Administration|banned substances]] in the United States.<ref name=":2" /><ref>{{Cite web|last=Pitts|first=Joseph R.|date=2014-12-18|title=Text - H.R.4771 - 113th Congress (2013-2014): Designer Anabolic Steroid Control Act of 2014|url=https://www.congress.gov/bill/113th-congress/house-bill/4771/text|access-date=2021-12-09|website=www.congress.gov}}</ref> |
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Examples of natural, human prohormones include [[proinsulin]] and [[pro-opiomelanocortin]]. |
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== Structure == |
== Structure == |
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Prohormones vary considerably in length and design, as do peptide hormones, but their base structure is the same.<ref name=":4">{{Cite journal|last=De Pablo|first=Flora|last2=de la Rosa|first2=Enrique|date=2011|title=Proinsulin: from hormonal precursor to neuroprotective factor|url=https://www.frontiersin.org/article/10.3389/fnmol.2011.00020|journal=Frontiers in Molecular Neuroscience|volume=4|pages=20|doi=10.3389/fnmol.2011.00020|issn=1662-5099}}</ref> They consist of one or more peptide hormones or hormone chains attached to each other in a way that prevents protein expression. |
Prohormones vary considerably in length and design, as do peptide hormones, but their base structure is the same.<ref name=":4">{{Cite journal|last=De Pablo|first=Flora|last2=de la Rosa|first2=Enrique|date=2011|title=Proinsulin: from hormonal precursor to neuroprotective factor|url=https://www.frontiersin.org/article/10.3389/fnmol.2011.00020|journal=Frontiers in Molecular Neuroscience|volume=4|pages=20|doi=10.3389/fnmol.2011.00020|issn=1662-5099}}</ref> They consist of one or more peptide hormones or hormone chains attached to each other in a way that prevents protein expression. |
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Some prohormones contain structures other than peptide hormones. For example, proinsulin contains an extra peptide called C-peptide that binds two insulin peptide chains together.<ref name=":4" /> |
Some prohormones contain structures other than peptide hormones. For example, proinsulin contains an extra peptide called C-peptide that binds two insulin peptide chains together, designed to keep both chains inactive .<ref name=":4" /> |
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== Function == |
== Function == |
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However, other inactive proteins travel in their prohormone form, such as [[vitamin D]], also known as calciferol, which can be produced by the human body via sunlight.<ref>{{Cite book|last=Calcium|first=Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D. and|url=https://www.ncbi.nlm.nih.gov/books/NBK56061/|title=Overview of Vitamin D|last2=Ross|first2=A. Catharine|last3=Taylor|first3=Christine L.|last4=Yaktine|first4=Ann L.|last5=Valle|first5=Heather B. Del|date=2011|publisher=National Academies Press (US)|language=en}}</ref> |
However, other inactive proteins travel in their prohormone form, such as [[vitamin D]], also known as calciferol, which can be produced by the human body via sunlight.<ref>{{Cite book|last=Calcium|first=Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D. and|url=https://www.ncbi.nlm.nih.gov/books/NBK56061/|title=Overview of Vitamin D|last2=Ross|first2=A. Catharine|last3=Taylor|first3=Christine L.|last4=Yaktine|first4=Ann L.|last5=Valle|first5=Heather B. Del|date=2011|publisher=National Academies Press (US)|language=en}}</ref> |
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The main regulator of prohormone to hormone conversion is [[prohormone convertase]]. Located in the Golgi apparatus, it uses endoproteolytic cleavage to separate peptide hormones from each other and removes extended amino acid residues that hinder the inactive peptides from being active proteins.<ref name=":1" /> Because of this role, prohormone convertase is one of the deciding factors for regulation of hormone content in the body, as it has the ability to change an inactive protein with unsubstantial hormonal effect on the body, to a fully active protein with a meaningful hormonal effect.<ref name=":1" /><ref>{{Cite journal|last=Nillni|first=Eduardo A.|date=2007-09-01|title=Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin |
The main regulator of prohormone to hormone conversion is [[prohormone convertase]]. Located in the Golgi apparatus, it uses endoproteolytic cleavage to separate peptide hormones from each other and removes extended amino acid residues that hinder the inactive peptides from being active proteins.<ref name=":1" /> Because of this role, prohormone convertase is one of the deciding factors for regulation of hormone content in the body, as it has the ability to change an inactive protein with unsubstantial hormonal effect on the body, to a fully active protein with a meaningful hormonal effect.<ref name=":1" /><ref>{{Cite journal|last=Nillni|first=Eduardo A.|date=2007-09-01|title=Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin |journal=Endocrinology|volume=148|issue=9|pages=4191–4200|doi=10.1210/en.2007-0173 |doi-access=free|issn=0013-7227}}</ref> |
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For [[Peptide hormone|peptide hormones]], the conversion process from prohormone to hormone ([[Protein precursor|pro-protein]] to [[protein]]) typically occurs after being exported to the [[endoplasmic reticulum]] and often requires multiple processing enzymes.<ref name=":3">{{Cite book|last=Alberts|first=Bruce |
For [[Peptide hormone|peptide hormones]], the conversion process from prohormone to hormone ([[Protein precursor|pro-protein]] to [[protein]]) typically occurs after being exported to the [[endoplasmic reticulum]] and often requires multiple processing enzymes.<ref name=":3">{{Cite book|last=Alberts|first=Bruce |title=Molecular biology of the cell|date=2002|publisher=Garland Science |author2=Alexander Johnson |author3=Julian Lewis |author4=Martin Raff |author5=Keith Roberts |author6=Peter Walter|isbn=0-8153-3218-1|edition=4th |location=New York|oclc=48122761}}</ref> [[Proamylin]], which is cosecreted with proinsulin, requires the above three factors and an amidating monooxygenase to convert itself to an active hormone.<ref>{{Cite journal|date=August 19, 2008|title=Amylin Proprotein Processing Generates Progressively More Amyloidogenic Peptides that Initially Sample the Helical State|journal=Biochemistry|volume=47|pages=9900-9910|via=American Chemical Society}}</ref> Some [[Preprohormone|pro-protein precursors]], such as [[preproinsulin]], also go through this process, with the added step of removing a signal peptide by [[Signal peptidase|signal peptidases]], to convert said precursors into prohormones.<ref name=":3" /> |
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== Uses == |
== Uses == |
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=== Prohormone supplements === |
=== Prohormone supplements === |
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The most everyday use of prohormones is as supplements for muscle growth via ergogenic and anabolic agents.<ref name=":6">{{Cite journal|last=Granados|first=Jorge|last2=Gillum|first2=Trevor L.|last3=Christmas|first3=Kevin M.|last4=Kuennen|first4=Matthew R.|date=2014-03-01|title=Prohormone supplement 3β-hydroxy-5α-androst-1-en-17-one enhances resistance training gains but impairs user health|url=https://journals.physiology.org/doi/full/10.1152/japplphysiol.00616.2013|journal=Journal of Applied Physiology|volume=116|issue=5|pages=560–569|doi=10.1152/japplphysiol.00616.2013|issn=8750-7587}}</ref> Prohormone supplements became popular from 1960 to 2001 before select prohormones such as androstenedione and androstenediol became banned in the United |
The most everyday use of prohormones is as supplements for muscle growth via ergogenic and anabolic agents.<ref name=":6">{{Cite journal|last=Granados|first=Jorge|last2=Gillum|first2=Trevor L.|last3=Christmas|first3=Kevin M.|last4=Kuennen|first4=Matthew R.|date=2014-03-01|title=Prohormone supplement 3β-hydroxy-5α-androst-1-en-17-one enhances resistance training gains but impairs user health|url=https://journals.physiology.org/doi/full/10.1152/japplphysiol.00616.2013|journal=Journal of Applied Physiology|volume=116|issue=5|pages=560–569|doi=10.1152/japplphysiol.00616.2013|issn=8750-7587}}</ref> Prohormone supplements became popular from 1960 to 2001 before select prohormones such as androstenedione and androstenediol became banned in the United States' Anabolic Steroid Control Act of 2004.<ref name=":6" /><ref>{{Cite web|date=2004-10-22|title=Text - S.2195 - 108th Congress (2003-2004): Anabolic Steroid Control Act of 2004|url=https://www.congress.gov/bill/108th-congress/senate-bill/2195/text|access-date=2021-12-09|website=www.congress.gov}}</ref> All prohormone supplements that were claimed to impart anabolic or ergogenic effects in men were banned for their poor side effects, which are as follows:<ref name=":6" /><ref name=":2" /> |
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* Acne |
* Acne |
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Revision as of 21:02, 10 December 2021
A prohormone is a committed precursor of a hormone consisting of peptide hormones synthesized together, having a minimal hormonal effect by itself because of its expression-suppressing structure.[1] Prohormones can travel the blood stream as a hormone in an inactivated form, ready to be activated later in the cell by post-translational modification.[1][2]
The body naturally produces prohormones as a way to regulate hormone expression, making them an optimal storage and transportation unit for inactive hormones. Once prohormones are needed to be expressed, prohormone convertase, a protein, cleaves the prohormones and separates them into one or more active hormones.[3] Often in nature, this cleaving process happens immediately, and a prohormone is quickly converted to a set of one or more peptide hormones.[4]
Examples of natural, human prohormones include proinsulin and pro-opiomelanocortin, but the most widespread prohormones in use are synthetic and labeled as anabolic steroid precursors, used as ergogenic or anabolic agents for muscle growth.[5] A commonly consumed example of said precursors are androstenedione and androstenediol, both of which are currently banned substances in the United States.[5][6]
Structure
Prohormones vary considerably in length and design, as do peptide hormones, but their base structure is the same.[7] They consist of one or more peptide hormones or hormone chains attached to each other in a way that prevents protein expression.
Some prohormones contain structures other than peptide hormones. For example, proinsulin contains an extra peptide called C-peptide that binds two insulin peptide chains together, designed to keep both chains inactive .[7]
Function
Prohormones allow for transport and storage of usually-active proteins as inactive peptide chains, though they are much more commonly found in nature as a stable intermediate in the protein-synthesizing process of the cell.[8] Proinsulin, for example, is seen in nature as a brief precursor to insulin, as it is produced on the ribosomes of the cell, transported to the Golgi apparatus as proinsulin, then is converted to insulin immediately after reaching the Golgi apparatus. It is also primarily stored as insulin.[4]
However, other inactive proteins travel in their prohormone form, such as vitamin D, also known as calciferol, which can be produced by the human body via sunlight.[9]
The main regulator of prohormone to hormone conversion is prohormone convertase. Located in the Golgi apparatus, it uses endoproteolytic cleavage to separate peptide hormones from each other and removes extended amino acid residues that hinder the inactive peptides from being active proteins.[3] Because of this role, prohormone convertase is one of the deciding factors for regulation of hormone content in the body, as it has the ability to change an inactive protein with unsubstantial hormonal effect on the body, to a fully active protein with a meaningful hormonal effect.[3][10]
For peptide hormones, the conversion process from prohormone to hormone (pro-protein to protein) typically occurs after being exported to the endoplasmic reticulum and often requires multiple processing enzymes.[11] Proamylin, which is cosecreted with proinsulin, requires the above three factors and an amidating monooxygenase to convert itself to an active hormone.[12] Some pro-protein precursors, such as preproinsulin, also go through this process, with the added step of removing a signal peptide by signal peptidases, to convert said precursors into prohormones.[11]
Uses
Prohormone supplements
The most everyday use of prohormones is as supplements for muscle growth via ergogenic and anabolic agents.[13] Prohormone supplements became popular from 1960 to 2001 before select prohormones such as androstenedione and androstenediol became banned in the United States' Anabolic Steroid Control Act of 2004.[13][14] All prohormone supplements that were claimed to impart anabolic or ergogenic effects in men were banned for their poor side effects, which are as follows:[13][5]
- Acne
- Hair loss
- Increased risk of heart disease
- Kidney and liver dysfunction
- Hypertension
- Impotence
In addition to this, research surrounding prohormones and prohormone supplements is limited, so many side effects are unknown regarding both legal and illegal prohormone supplements.[13][5]
See also
References
- ^ a b Friedman, Theodore C.; Cool, David R. (2004-01-01), Martini, Luciano (ed.), "Prohormones", Encyclopedia of Endocrine Diseases, New York: Elsevier, pp. 91–98, doi:10.1016/b0-12-475570-4/01074-x, ISBN 978-0-12-475570-3, retrieved 2021-12-04
- ^ Miller, Benjamin Frank; Claire Brackman Keane (1997). Miller-Keane Encyclopedia & dictionary of medicine, nursing & allied health (6th ed.). Philadelphia: Saunders. ISBN 0-7216-6278-1. OCLC 36465055.
- ^ a b c Dhanvantari, Savita; Cawley, Niamh X.; Loh, Y. Peng (2004-01-01), Martini, Luciano (ed.), "Prohormone Convertases", Encyclopedia of Endocrine Diseases, New York: Elsevier, pp. 84–90, ISBN 978-0-12-475570-3, retrieved 2021-12-09
- ^ a b Alarcon, Cristina; Wicksteed, Barton; Rhodes, Christopher J. (2003-01-01), Henry, Helen L.; Norman, Anthony W. (eds.), "Insulin Processing", Encyclopedia of Hormones, New York: Academic Press, pp. 359–368, doi:10.1016/b0-12-341103-3/00175-3, ISBN 978-0-12-341103-7, retrieved 2021-12-09
- ^ a b c d Powers, Michael E. (2002). "The Safety and Efficacy of Anabolic Steroid Precursors: What is the Scientific Evidence?". Journal of Athletic Training. 37 (3): 300–305. ISSN 1062-6050. PMID 16558675.
- ^ Pitts, Joseph R. (2014-12-18). "Text - H.R.4771 - 113th Congress (2013-2014): Designer Anabolic Steroid Control Act of 2014". www.congress.gov. Retrieved 2021-12-09.
- ^ a b De Pablo, Flora; de la Rosa, Enrique (2011). "Proinsulin: from hormonal precursor to neuroprotective factor". Frontiers in Molecular Neuroscience. 4: 20. doi:10.3389/fnmol.2011.00020. ISSN 1662-5099.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Goetze, Jens P (August 6, 2009). "Peptide hormones and their prohormones as biomarkers". Biomarkers in Medicine. 3 – via Future Medicine.
- ^ Calcium, Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D. and; Ross, A. Catharine; Taylor, Christine L.; Yaktine, Ann L.; Valle, Heather B. Del (2011). Overview of Vitamin D. National Academies Press (US).
- ^ Nillni, Eduardo A. (2007-09-01). "Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin". Endocrinology. 148 (9): 4191–4200. doi:10.1210/en.2007-0173. ISSN 0013-7227.
- ^ a b Alberts, Bruce; Alexander Johnson; Julian Lewis; Martin Raff; Keith Roberts; Peter Walter (2002). Molecular biology of the cell (4th ed.). New York: Garland Science. ISBN 0-8153-3218-1. OCLC 48122761.
- ^ "Amylin Proprotein Processing Generates Progressively More Amyloidogenic Peptides that Initially Sample the Helical State". Biochemistry. 47: 9900–9910. August 19, 2008 – via American Chemical Society.
- ^ a b c d Granados, Jorge; Gillum, Trevor L.; Christmas, Kevin M.; Kuennen, Matthew R. (2014-03-01). "Prohormone supplement 3β-hydroxy-5α-androst-1-en-17-one enhances resistance training gains but impairs user health". Journal of Applied Physiology. 116 (5): 560–569. doi:10.1152/japplphysiol.00616.2013. ISSN 8750-7587.
- ^ "Text - S.2195 - 108th Congress (2003-2004): Anabolic Steroid Control Act of 2004". www.congress.gov. 2004-10-22. Retrieved 2021-12-09.