Direct effect of plasma sex hormone binding globulin (SHBG) on the metabolic clearance rate of 17 beta-estradiol in the primate.
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.
Plymate
S R
SR
Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA 98431-5454.
Namkung
P C
PC
Metej
L A
LA
Petra
P H
PH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D004958:Estradiol / Q000097:blood*; D007116:Immunization, Passive; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood; D008254:Macaca nemestrina; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011485:Protein Binding; D012738:Sex Hormone-Binding Globulin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D000906:Antibodies; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone