Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells
Abstract
OBJECTIVES: 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.
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These data suggest that E4 in combination with DRSP has a low estrogenic effect, in particular on the liver.
“These data suggest that E4 in combination with DRSP has a low estrogenic effect, in particular on the liver [ 15 , 20 ].”
From Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone (2021) · cites this paper as [20]
Previous observations have shown that E4 slightly increases SHBG.
“Previous observations have shown that E4 slightly increases SHBG.”
From Endocrine and metabolic effects of an oral contraceptive containing estetrol and drospirenone (2021) · cites this paper as [20]
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- Authors
- Hammond, G. L., Hogeveen, K. N., Visser, M., & Coelingh Bennink, H. J. T.
- Affiliations
- University of British Columbia (CA)
- Inserm (FR)
- Pantarhei Bioscience (Netherlands) (NL)
- Venue
- Climacteric
- Publisher
- Informa UK Limited
- Published
- 2008-01
- Volume
- 11
- Issue
- sup1
- Pages
- 41-46
- ISSN
- 1369-7137 (ISSN-L)
- 1473-0804
- OpenAlex
- W2073107954
- Cited by
- 65
- References
- 8
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 10 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Climacteric (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- estetrol, sex hormone-binding globulin, estrogen receptor alpha, HepG2 cells, hepatocytes, ethinyl estradiol, estradiol, estriol, testosterone
- MeSH terms
- Estetrol, Female, Humans, Kinetics, Ligands, Sex Hormone-Binding Globulin, Tritium, Tumor Cells, Cultured, Estrogen Receptor alpha
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