The high-affinity binding of the sex hormone-binding globulin (SHBG) for testosterone
and to a lesser extent for estradiol influences the circulating levels of these sex
steroid hormones, their biodisposal to target cells as well as their mutual balance.
Although the regulation of SHBG is still not completely understood, in vitro studies
performed with human hepatocarcinoma (Hep G2) cells have shown that estrogens and
thyroxine stimulate SHBG secretion, by increasing the steady state of its mRNA concentrations.
These observations are in good agreement with studies showing that SHBG levels increase
during oral administration of estrogens as well as in patients with thyrotoxicosis.
Interestingly, SHBG levels are normal in syndromes such as the abnormal transport
of thyroid hormones and/or the syndrome of thyroid hormone resistance, which can be
confused with thyrotoxicosis. By constrast, the effects of androgens are controversial.
In many patients with hirsutism, SHBG concentrations are low and correlate negatively
with both body mass index and fasting insulin levels. Because of the inhibitory effect
of both insulin and insulinlike growth factor-1 on SHBG secretion by Hep G2 cells
in vitro, it has been proposed that SHBG levels could be a marker of insulin resistance
and/or hyperinsulinism in humans. Furthermore, an increased risk for either noninsulin-dependent
diabetes and/or the overall mortality are associated with decreased SHBG levels in
postmenopausal women. Finally, in men, SHBG levels are positively correlated with
the concentration of high-density lipoprotein cholesterol. Therefore, the measurement
of SHBG in clinical practice can be a useful diagnostic tool for: (1) correctly interpretating
testosterone and estradiol serum concentrations; (2) investigating androgen-estrogen
balance in gonadal and sexual dysfunctions; (3) assessing the peripheral effect of
the hormones which regulate SHBG productions, and (4) evaluating insulin resistance
and cardiovascular risk.