Pharmacological effects of 2- and 4-methyloestradiol as a probe to test the biological importance of 2- and 4-hydroxylation of oestrogens (catecholoestrogen-formation).
2-Methyloestradiol, 4-hydroxy-2-methyloestradiol and 4-methyloestradiol were synthesized and infused sc into long-term ovariectomized rats by means of osmotic minipumps. The effects on uterine growth and gonadotrophin release were tested and compared to oestradiol or vehicle alone. 2-Methyloestradiol and 4-hydroxy-2-methyloestradiol, steroids in which the 2-hydroxylation is selectively blocked, definitely increased uterine weight (dry and wet), decreased morning LH and increased evening LH serum levels. 4-Methyloestradiol, a compound which cannot be 4-hydroxylated in vivo, was inactive in the model used. It is assumed that 4-hydroxylation constitutes an essential step in the expression of oestrogenicity of primary oestrogens, whereas 2-hydroxylation does not.
D000818:Animals; D002369:Castration; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000096:biosynthesis*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D006900:Hydroxylation; D007986:Luteinizing Hormone / Q000097:blood*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects*
D002393:Estrogens, Catechol; C037233:2-methylestradiol; D004970:Estrone; D004958:Estradiol; C037235:4-hydroxy-2-methylestradiol; D007986:Luteinizing Hormone; C037234:4-methylestradiol