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

OBJECTIVE: Sex hormone-binding globulin (SHBG) binds testosterone (T) to a greater degree than it does estradiol (E-2), acting as an amplifier of E-2 action. However; it is not known whether the relative capacity of SHBG for E-2 vs. T is altered by the hormonal milieu. We hypothesized that an increase in circulating E-2 levels results in a compensatory increase in the relative binding capacity of SHBG for these hormones, dampening the E-2 amplification effect in hyperestrogenic conditions. STUDY DESIGN: Retrospective. RESULTS: As expected, during hMG stimulation there was a significant increase in fetal and free E-2 (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 E-2 and T increased in a proportional manner (980 +/- 340 vs. 1,434 +/- 449 nmol/L, P < .009; and 352 +/- 290 vs. 512 +/- 128 nmol/L, P < .02; respectively) since the ratio of SHBG binding to E-2 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). CONCLUSION: A short-term, although profound, increase in circulating E-2 does not seem to be associated with an increase in the relative binding capacity of the carrier protein for either E-2 or T, although an overall increase in binding for both steroids ions observed. It is possible that longer periods of exposure to E-2 may be necessary to demonstrate a change in the differential binding of this carrier protein with an alteration in the hormonal milieu.