Pharmacological effects of 2- and 4-methyloestradiol as a probe to test the biological importance of 2- and 4-hydroxylation of oestrogens (catecholoestrogen-formation)

Abstract

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.