Direct effect of plasma sex hormone binding globulin (SHBG) on the metabolic clearance rate of 17β-estradiol in the primate

Abstract

Sex hormone binding globulin (SHBG) has been shown to be a major determinant of testosterone clearance in the primate. It has also been suggested that SHBG would also be a determinant of estradiol clearance (MCR-E₂). However, published studies have suggested that the MCR-E₂ do not always vary with changes in the level of SHBG. Therefore, the present study was undertaken to address this issue. The baseline MCR-E₂ was determined in adult male pigtail macaques (Macaca nemestrina). Following the baseline determination of MCR-E₂ the animals were infused with either purified human (h)SHBG or antibody against hSHBG, which also has a high degree of cross-reactivity with primate SHBG. Following the infusions of either hSHBG or anti-SHBG, MCR-E₂ was again determined. In addition, luteinizing hormone (LH) was measured using a mouse Leydig cell bioassay. Following the infusion of hSHBG, a marked increase in serum SHBG was noted and the MCR-E₂ decreased. Associated with the increase in SHBG, the SHBG bound T levels decreased and LH increased. Following the infusion of antibody, serum SHBG decreased, and the MCR-E₂ also decreased. With the decrease in SHBG following the antibody infusion, non-SHBG bound T increased and serum LH fell. This study demonstrates that an increase in the serum SHBG levels is associated with a decrease in MCR-E₂, however, an acute decrease in serum SHBG also decreases the MCR-E₂. This later result demonstrates that factors in addition to serum SHBG binding may be important in determining the MCR-E₂.