Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells.
OBJECTIVE
To determine whether human sex hormone binding globulin (SHBG) binds estetrol (E4), and to assess whether E4 stimulates the production of SHBG by human hepatocytes.


METHODS
Competitive ligand binding assays have been used to assess the relative binding affinity of E4 to human SHBG using either [3H]5alpha-dihydrotestosterone or [3H]estradiol as labeled ligands. The effect of E4 on the production of SHBG has been assessed by a fluoroimmunometric assay in wild-type human HepG2 cells and in human Hep89 cells that over-express the human estrogen receptor (ER) alpha, and compared to the effect of ethinylestradiol, estradiol and estriol.


RESULTS
There was no detectable binding of E4 to the human SHBG steroid-binding sites. By contrast, testosterone and estradiol were bound with high affinity and the synthetic estrogen ethinylestradiol was found to bind SHBG with low affinity. Estetrol does not stimulate ERalpha-mediated increases in SHBG production by HepG2 or Hep89 cells, in contrast to ethinylestradiol, estradiol and estriol.


CONCLUSIONS
These data indicate that SHBG has no influence on the plasma distribution of E4 or its availability to target tissues. In addition, it is shown that E4 has no effect on SHBG production by human hepatocytes.
Hammond
G L
GL
Department of Obstetrics and Gynecology, University of British Columbia, and Child and Family Research Institute, Vancouver, Canada.
Hogeveen
K N
KN
Visser
M
M
Coelingh Bennink
H J T
HJ
D004953:Estetrol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008024:Ligands; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D008024:Ligands; D012738:Sex Hormone-Binding Globulin; D014316:Tritium; D004953:Estetrol