Sex hormone-binding globulin
) is a glycoprotein
that binds to sex hormones
, specifically testosterone
. Other steroid hormones
such as progesterone
, and other corticosteroids
are bound by transcortin
Transport of sex hormones
These sex hormones circulate in the bloodstream, bound mostly to SHBG and to some degree bound to serum albumin
. Only a small fraction is unbound, or "free," and thus biologically active and able to enter a cell
and activate its receptor
. The SHBG inhibits the function of these hormones. Thus bioavailability of sex hormones is influenced by the level of SHBG.
SHBG is produced by the liver
cells and is released into the bloodstream. Other sites that produce SHBG are the brain, uterus, and placenta and vagina. In addition SHBG is produced by the testes; testes-produced SHBG is also called androgen-binding protein
. The gene
for SHBG is located on chromosome
SHBG levels appear to be controlled by a delicate balance of enhancing and inhibiting factors. Its level is decreased by high levels of insulin
and insulin-like growth factor 1 (IGF-1
). Also, high androgen
levels decrease SHBG, while high estrogen
levels increase it.
However, recent evidence suggests that it is the liver's production of fats that reduces SHBG levels, not any direct effect of insulin and specific genetic mechanisms have been found that do this.
Conditions with high or low levels
Conditions with low SHBG include polycystic ovary syndrome
, and hypothyroidism
. Conditions with high SHBG include pregnancy
, and anorexia nervosa
. There has recently been research to link high SHBG levels with breast and testicular cancer as well.
Measurement of sex hormones
When determining levels of circulating estradiol or testosterone, either a total measurement could be done that includes the "free" and the bound fractions, or only the "free" hormone could be measured.
A free androgen index
expresses the ratio of testosterone to the sex hormone binding globulin and can be used to summarise the activity of free testosterone.
The total testosterone is likely the most accurate measurement of testosterone levels and should always be measured at 8 o'clock in the morning. Sex hormone binding globulin can be measured separate from the total fraction of testosterone.