The SHBG1 gene is one of the genes used in combination to determine your testosterone levels. Sex-hormone binding gobulin (SHBG) levels are regulated through this gene. This protein is involved in the transport of sex hormones which is how it can influence the levels of circulating testosterone.


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Global population distribution:

Source: 1000 Genome Project. Global averages for both sexes

SHBG1: AA

2%

SHBG1: GA

16%

SHBG1: GG

82%

More about SHBG1

Testosterone can be found in the bloodstream bound to a protein called the sex hormone-binding globulin (SHBG). Testosterone can also be weakly bound to albumin, as well as freely circulating in the blood as an unbound molecule. Previously, SHBG-bound testosterone was thought to be inactive while albumin-bound testosterone was classed as partially bioavailable and free testosterone as available; these available fractions were thought to represent the pools of testosterone that are able to exert an effect on the cells in the body. To this end, higher SHBG levels were thought to be detrimental to testosterone activity as they lead to increased pools of bound testosterone, thus reducing free and active testosterone. However, the relationship between testosterone and SHBG is now being revisited, with increasing evidence showing SHBG has an active role in steroid function.

Firstly, it has been shown that SHBG can bind to, be taken up by and synthesised by many cells in the body. It was originally thought to be produced by just the liver and circulated in the blood. Further to this, data suggests SHBG may be able to promote, not repress, steroid binding and activity. The way this occurs varies in different cell types and involves the recruitment of additional steroids that in turn promote parallel signalling pathways.

Additional fluctuations in SHBG levels occur during ageing, and these may be caused by reductions in both growth hormone and insulin function. Finally, natural SHBG variations can also occur due to lifestyle changes and activities. The relationship between testosterone and SHBG is therefore complex. In spite of this, low SHBG and low testosterone levels — independently and combined — have been linked to poor body composition, obesity, and metabolic dysfunction. This suggests that actions which promote good testosterone and SHBG levels are both beneficial for longevity. Therefore, we look at genetic variants that affect both.

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