Prohormone
A prohormone is a committed
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,
Examples of natural, human prohormones include
Structure
Prohormones vary considerably in length and design, as do peptide hormones, but their base structure is the same.[1][9] They consist of one or more inactive peptide hormones or hormone chains attached to each other in a way that prevents hormone expression, often by making the chains’ binding ends inaccessible via folding and binding of other chains to said ends.[9] For hormonal expression to be induced, the binding ends of hormones but either bind to receptors in the cell membrane, or in the case of steroids, bind to steroid receptor proteins in the cell, both of which mediate hormone expression.[2]
Some prohormones contain structures other than inactive peptide hormones for the purpose of keeping hormone expression suppressed. For example, proinsulin contains an extra non-hormonal chain called C-peptide that binds two insulin peptide chains together, designed to keep both chains inactive by binding to their ends, specifically, their C-domain junctions, which have been proposed to be their site of binding to hormone-expression receptors in the cell.[9] Despite the restrictions it enables, the C-peptide folds the proinsulin chains to make their junction ends accessible to be cleaved by prohormone convertases later, making the folding of the proinsulin chain containing C-peptide essential for the proper cleavage of proinsulin to successfully produce insulin.[10]
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.[11] 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.[5]
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.[12]
The main regulator of prohormone to hormone conversion is
For
Uses
Prohormone supplements
The most everyday use of prohormones is as supplements for muscle growth via ergogenic and anabolic agents.[16] Prohormone supplements became popular from 1960 to 2001 and became used unregulated in Major League Baseball before select prohormones such as androstenedione and androstenediol became banned in the United States' Anabolic Steroid Control Act of 2004.[16][17] Many prohormone supplements that were claimed to impart anabolic or ergogenic effects in men were banned for their poor side effects, commonly in supplements such as in 3β-hydroxy-5α-androst-1-en-17-one, commonly known as 1-testosterone, which are as follows:[16][6]
- Acne
- Hair loss
- Increased risk of heart disease
- Kidney and liver dysfunction
- Hypertension
- Impotence
Many prohormone supplements such as 1-testosterone were legal in the United States until reclassified as a
Research surrounding other prohormones and prohormone supplements is limited, so many side effects are unknown regarding both legal and illegal prohormone supplements.[16][6]
See also
References
- ^ ISBN 978-0-12-475570-3, retrieved 2021-12-04
- ^ a b "Control of Gene Expression in Eukaryotes". www.ndsu.edu. Retrieved 2021-12-10.
- OCLC 36465055.
- ^ ISBN 978-0-12-475570-3, retrieved 2021-12-09
- ^ ISBN 978-0-12-341103-7, retrieved 2021-12-09
- ^ 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.
- ^ S2CID 4942690.
- ^ PMID 21949502.
- PMID 31184302.
- PMID 20477480– 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).
- PMID 17584972.
- ^ OCLC 48122761.
- PMID 18710262– via American Chemical Society.
- ^ PMID 24381122.
- ^ a b "Text - S.2195 - 108th Congress (2003-2004): Anabolic Steroid Control Act of 2004". www.congress.gov. 2004-10-22. Retrieved 2021-12-09.