In an attempt to define pharmacological probes with which to test the role of catechol oestrogen formation in the central nervous system, five oestrogens (oestradiol-17β, oestradiol-17α, 4-fluoro-oestradiol, 2-fluoro-oestradiol and moxestrol (11β-methoxy-17α-ethynyloestradiol)) were studied for binding to oestrogen receptors and conversion to catechol metabolites. Binding to cytosol oestrogen receptors was measured in the hypothalamus-preoptic area-amygdala (HPA), pituitary gland and uterus of ovariectomized rats. Conversion to catechol oestrogens was tested in microsomes from the HPA, pituitary gland and liver, using a catechol-O-methyltransferase-coupled radioenzymatic assay. Oestradiol-17α was the only weak oestrogen receptor ligand. Binding affinities of the other compounds tested were much higher and comparable to those of oestradiol-17β. In contrast, oestradiol-17α was rapidly converted to catechol metabolites, while moxestrol was a relatively poor substrate for catechol oestrogen formation. 4-Fluoro-oestradiol could be 2-hydroxylated but not 4-hydroxylated. 2-Fluoro-oestradiol exhibited impaired 2-hydroxylation but normal 4-hydroxylation.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism