Testosterone-estradiol binding globulin binds to 2-methoxyestradiol with greater affinity than to testosterone.
Level 5 - mechanism / opinion, no new human data
In vitro bench/binding study with no human clinical data
PubMed 7190578 · doi:10.1210/jcem-51-2-404
What was done
The authors measured the relative binding affinity of 2-methoxyestradiol, testosterone, and 17 beta-estradiol to testosterone-estradiol binding globulin (TeBG) using competitive displacement of [3H]-testosterone on a solid-phase Con A-Sepharose matrix. They also evaluated 2-methoxyestradiol binding to the androgen receptor via competitive displacement of [3H]-dihydrotestosterone in 64-24 rat mammary tumor cells.
What was found
The relative binding activities for TeBG were 2.0 for 2-methoxyestradiol, 1.0 for testosterone, and 0.32 for 17 beta-estradiol. 2-Methoxyestradiol showed only low-affinity binding to the androgen receptor, paralleling its established low affinity for estrogen receptors.
Why it matters
This identified 2-methoxyestradiol as the first known endogenous steroid that binds with higher affinity to TeBG (SHBG) than testosterone while exhibiting minimal affinity for classical androgen and estrogen receptors.
Limits
The abstract describes exclusively in vitro competitive binding assays and does not report sample sizes, replicate numbers, or assay variability metrics. In vivo physiological consequences, plasma protein distribution, and metabolic clearance were not evaluated.
Cited by
- supports Dihydrotestosterone (DHT) has a higher binding affinity for SHBG than testosterone, and testosterone has a higher binding affinity for SHBG than estrogen.