Differential binding of estradiol and testosterone to SHBG. Relation to circulating estradiol levels

Sex hormone-binding globulin (SHBG) binds testosterone (T) to a greater degree than it does estradiol (E2), acting as an amplifier of E2 action. However, it is not known whether the relative capacity of SHBG for E2 vs. T is altered by the hormonal milieu. We hypothesized that an increase in circulating E2 levels results in a compensatory increase in the relative binding capacity of SHBG for these hormones, dampening the E2 amplification effect in hyperestrogenic conditions.

Retrospective.

As expected, during hMG stimulation there was a significant increase in total and free E2 (28 to 1,986 pg/mL, P < .001; and 0.3 to 20.8 pg/mL, P < .001, respectively) and total T levels (40.3 vs. 78.3 ng/dL, P < .001) from basal to late stimulation. Free T levels increased, but the difference did not reach significance. The binding capacity of SHBG for both E2 and T increased in a proportional manner (980 +/- 340 vs. 1,434 +/- 449 nmol/L, P < .009; and 352 +/- 190 vs. 512 +/- 128 nmol/L, P < .02; respectively) since the ratio of SHBG binding to E2 and T was unchanged. Although the SHBG molar concentration appeared increased, the difference did not reach significance (821 +/- 542 to 1,099 +/- 254 nmol/L).

A short-term, although profound, increase in circulating E2 does not seem to be associated with an increase in the relative binding capacity of the carrier protein for either E2 or T, although an overall increase in binding for both steroids was observed. It is possible that longer periods of exposure to E2 may be necessary to demonstrate a change in the differential binding of this carrier protein with an alteration in the hormonal milieu.