The androgen hormone testosterone drives the production of sperm in the testicles and promotes the development of typical male characteristics. Women also produce testosterone, but in much lower amounts. Secreted into the blood, testosterone circulates until it reaches its target tissues, where it binds to androgen receptors to relay its signal into cellular effects. In the circulation, most testosterone molecules link tightly to escort molecules and are considered "bound." Other molecules of testosterone circulate unescorted, or "free."
Definitions
Scientists can measure different pools or "fractions" of total testosterone circulating in the blood. "Bound" testosterone refers to testosterone molecules that circulate in the blood tightly bound to a protein molecule called sex hormone binding globulin, or SHBG. Testosterone molecules can also circulate partnered with an abundant component of blood called albumin. The link between testosterone and albumin is so weak that this fraction is not considered "bound." Testosterone can also circulate alone, and this fraction is considered "free."Confusingly, the term "free" sometimes encompass both the unbound and the albumin-linked fractions of testosterone, because both can enter cells.
Statistics
According to Quest Diagnostics, approximately 60 to 70 percent of testosterone in the blood binds to SHBG. Another 30 to 40 percent of circulating testosterone partners with albumin, and only about 2 percent circulates by itself in the free form.
Significance
Testosterone exerts its effects by binding to androgen receptors inside its target tissues. Only biologically available testosterone, meaning the fraction can enter the cells, can produce any effects. The bond between testosterone and SHBG is so strong that the testosterone cannot enter the cells and interact with the androgen receptors, so the fraction of testosterone bound to SHBG is considered biologically unavailable, although eventually the bond will break. In contrast, free testosterone and albumin-linked testosterone are biologically available. Free testosterone readily enters cells, and the link between testosterone and albumin is so weak that it rapidly falls apart, allowing access to the cells.
Measurement
Simple laboratory tests of blood samples can measure the total circulating level of testosterone and give a rough idea of the potential biological effects. More extensive tests on blood can differentiate between the amount of testosterone that is bound to SHBG and unavailable for use versus the amount that is free and biologically active.
Considerations
Certain medical conditions can alter the level of SHBG in the blood and the proportion of SHBG bound testosterone. According to "Endocrinology: An Integrated Approach," too much thyroid hormone increases levels of SHBG, whereas too little thyroid hormone decreases levels of SHBG. Liver damage from cirrhosis decreases the amount of SHBG. An excess of growth hormone and obesity both decrease the level of SHBG. Some women who suffer from hirsutism, or excess body hair, have normal levels of total testosterone but higher levels of bioavailable testosterone.
References
- "Endocrinology: An Integrated Approach"; Stephen Nussey and Saffron; 2001
- Quest Diagnostics: Testosterone, LC/MS/MS
