Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? I. Characterization of pharmacological probes with different receptor binding affinities and catechol oestrogen formation rates

D. G. Pfeiffer, N. J. MacLusky, E. Barnea, F. Naftolin, L. C. Krey, Donald (Lynn) Loriaux, G. R. Merriam

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)489-497
Number of pages9
JournalJournal of Endocrinology
Volume110
Issue number3
StatePublished - 1986
Externally publishedYes

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Catechol Estrogens
Estradiol
Estrogens
Central Nervous System
Pharmacology
Estrogen Receptors
Preoptic Area
Pituitary Gland
Hydroxylation
Amygdala
Hypothalamus
Catechol O-Methyltransferase
Microsomes
Cytosol
Uterus
Ligands

ASJC Scopus subject areas

  • Endocrinology

Cite this

Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? I. Characterization of pharmacological probes with different receptor binding affinities and catechol oestrogen formation rates. / Pfeiffer, D. G.; MacLusky, N. J.; Barnea, E.; Naftolin, F.; Krey, L. C.; Loriaux, Donald (Lynn); Merriam, G. R.

In: Journal of Endocrinology, Vol. 110, No. 3, 1986, p. 489-497.

Research output: Contribution to journalArticle

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