Catechol estrogen formation and metabolism in brain tissue: comparison of tritium release from different positions in ring A of the steroid

Journal Article · Thu Nov 01 04:00:00 EST 1984 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-115-5-1850· OSTI ID:5948084

Jellinck, P H; Hahn, E F; Norton, B I; Fishman, J

Catechol estrogens labeled with /sup 3/H at different positions in rings A and B of the steroid were synthesized by chemical or enzymatic methods, and their oxidative transformation by male rat brain microsomes was followed by the transfer of /sup 3/H into /sup 3/H/sub 2/O. This reaction was shown to occur more readily with the catechol estrogens than with the parent steroid and was also influenced by the position of the radiolabel. Tritium was displaced less readily from C-1 than from C-2 or C-4 of the aromatic ring. Spermine, which is known to increase cytochrome P-450-mediated hydroxylation reactions, had no effect on the release of /sup 3/H from ring A of either estradiol or 2-hydroxyestradiol with rat brain microsomes in contrast to liver. Glutathione and other thiols were able to cause a rapid loss of /sup 3/H from labeled catechol estrogens, even in the absence of tissue, but in double label experiments with (4-/sup 3/H)- and (4-/sup 14/C)2-hydroxyestradiol, the isotope ratio in the recovered catechol estrogen was unchanged. The results illustrate some of the problems in determining accurately the metabolism of estrogens by measuring /sup 3/H/sub 2/O formation when aromatic hydroxylation is involved and also highlight the possible interaction of the catechol estrogens with cellular nucleophiles such as glutathione.

• Research Organization: Rockefeller Univ., New York, NY
• OSTI ID: 5948084
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 115:5; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
BRAIN
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
COMPARATIVE EVALUATIONS
CYTOCHROMES
DEVELOPERS
DRUGS
ESTRADIOL
ESTRANES
ESTROGENS
GLUTATHIONE
HORMONES
HYDROXY COMPOUNDS
HYDROXYLATION
ISOTOPE APPLICATIONS
ISOTOPE RATIO
KINETICS
LABELLED COMPOUNDS
LABELLING
MAMMALS
METABOLIC ACTIVATION
METABOLISM
MICROSOMES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANOIDS
ORGANS
PEPTIDES
PHENOLS
PIGMENTS
POLYPEPTIDES
POLYPHENOLS
PROTEINS
PYROCATECHOL
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RODENTS
SPERMINE
STEROID HORMONES
STEROIDS
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
THIOLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES