Editing Testosterone (section)

===Free testosterone===
[[Lipophilic]] [[hormones]] (soluble in [[lipids]] but not in [[water]]), such as [[steroid]] hormones, including testosterone, are transported in water-based [[blood plasma]] through specific and non-specific [[proteins]]. Specific proteins include [[sex hormone-binding globulin]] (SHBG), which binds testosterone, [[dihydrotestosterone]], [[estradiol]], and other [[sex steroids]]. Non-specific binding proteins include [[albumin]]. The part of the total hormone concentration that is not bound to its respective specific carrier protein is the free part. As a result, testosterone which is not bound to SHBG is called ''free testosterone''. Only the free amount of testosterone can bind to an androgenic receptor, which means it has biological activity.<ref name="pmid33553985">{{cite journal |vauthors=Bikle DD |title=The Free Hormone Hypothesis: When, Why, and How to Measure the Free Hormone Levels to Assess Vitamin D, Thyroid, Sex Hormone, and Cortisol Status |journal=[[JBMR Plus]] |volume=5 |issue=1 |pages=e10418 |date=January 2021 |pmid=33553985 |pmc=7839820 |doi=10.1002/jbm4.10418 |url= }}</ref> While a significant portion of testosterone is bound to SHBG, a small fraction of testosterone (1%-2%)<ref name="synevo"/> is bound to albumin and the binding of testosterone to albumin is weak and can be reversed easily;<ref name="pmid30842823"/><ref name="pmid28673039"/> as such, both albumin-bound and unbound testosterone are considered to be bioavailable testosterone.<ref name="pmid30842823"/><ref name="pmid28673039"/> This binding plays an important role in regulating the transport, tissue delivery, bioactivity, and metabolism of testosterone.<ref name="pmid28673039">{{cite journal |vauthors=Goldman AL, Bhasin S, Wu FC, Krishna M, Matsumoto AM, Jasuja R |title=A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications |journal=Endocr Rev |volume=38 |issue=4 |pages=302–324 |date=August 2017 |pmid=28673039 |pmc=6287254 |doi=10.1210/er.2017-00025 |url=}}</ref><ref name="pmid30842823">{{cite journal |vauthors=Czub MP, Venkataramany BS, Majorek KA, Handing KB, Porebski PJ, Beeram SR, Suh K, Woolfork AG, Hage DS, Shabalin IG, Minor W |title=Testosterone meets albumin - the molecular mechanism of sex hormone transport by serum albumins |journal=Chem Sci |volume=10 |issue=6 |pages=1607–1618 |date=February 2019 |pmid=30842823 |pmc=6371759 |doi=10.1039/c8sc04397c |url=}}</ref> At the tissue level, testosterone dissociates from albumin and quickly diffuses into the tissues. The percentage of testosterone bound to SHBG is lower in men than in women. Both the free fraction and the one bound to albumin are available at the tissue level (their sum constitutes the bioavailable testosterone), while SHBG effectively and irreversibly inhibits the action of testosterone.<ref name="synevo"><!--sorry, could not find a better source that would have been accessible -->{{cite web|url=https://www.synevo.md/shop/testosteron-liber/|title=Testosteron liber|language=ro|trans-title=Free testosterone|publisher=Synevo Moldova|access-date=March 30, 2024|archive-date=January 29, 2023|archive-url=https://web.archive.org/web/20230129153430/https://www.synevo.md/shop/testosteron-liber/|url-status=live}}</ref> The relationship between sex steroids and SHBG in physiological and pathological conditions is complex, as various factors may influence the levels of plasma SHBG, affecting bioavailability of testosterone.<ref name="pmid4062218">{{cite journal |vauthors=Cunningham SK, Loughlin T, Culliton M, McKenna TJ |title=The relationship between sex steroids and sex-hormone-binding globulin in plasma in physiological and pathological conditions |journal=Ann Clin Biochem |volume=22|issue= 5|pages=489–97 |date=September 1985 |pmid=4062218 |doi=10.1177/000456328502200504 |url=}}</ref><ref name="pmid33139661">{{cite journal |vauthors=Qu X, Donnelly R |title=Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome |journal=Int J Mol Sci |volume=21 |issue=21 |date=November 2020 |page=8191 |pmid=33139661 |pmc=7663738 |doi=10.3390/ijms21218191|doi-access=free }}</ref><ref name="pmid34197576">{{cite journal |vauthors=Aribas E, Kavousi M, Laven JS, Ikram MA, Roeters van Lennep JE |title=Aging, Cardiovascular Risk, and SHBG Levels in Men and Women From the General Population |journal=J Clin Endocrinol Metab |volume=106 |issue=10 |pages=2890–2900 |date=September 2021 |pmid=34197576 |pmc=8475196 |doi=10.1210/clinem/dgab470 }}</ref>