Neonatal defeminization of the luteinizing hormone release mechanism by catecholestrogens: different potencies of 2- and 4-hydroxyestradiol.
Female rats were neonatally treated with estradiol-17 beta-benzoate or the long-acting dibenzoate esters of the isomeric catecholestrogens, 2-hydroxyestradiol-17 beta and 4-hydroxyestradiol-17 beta. Estrogen benzoates were administered subcutaneously from day 1 to 5 of life at doses of 0.05, 0.10, 0.50 and 1.00 micrograms/day. All rats were ovariectomized as adults and, 4 weeks later, the luteinizing hormone (LH) response to progesterone (2.5 mg) was tested after priming with estradiol-17 beta-benzoate (20 micrograms). At a dose of 0.5 micrograms/day, estradiol-17 beta-benzoate and 4-hydroxyestradiol-17 beta-dibenzoate were equally effective in neonatally defeminizing the LH surge mechanism. In contrast, up to a dose of 1.00 micrograms/day, 2-hydroxyestradiol-17 beta-dibenzoate did not interfere with the LH response in adult life. In the pituitary gland and uterus of the neonatally defeminized rats estrogen responsiveness of cytosolic progestin receptor induction was unimpaired. Moreover, in the uterus of these rats nuclear translocation of cytosolic progestin receptors was intact.
D000818:Animals; D000831:Animals, Newborn; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D002393:Estrogens, Catechol; D011980:Receptors, Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol