Long-acting estrogenic responses of estradiol fatty acid esters.
Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesized and then evaluated for their long-acting estrogenic responses in ovariectomized rats. The duration of the biological effects was measured after a single subcutaneous dose of 0.1 mumol of each ester and compared with those observed with 17 beta-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17 beta-estradiol levels were measured 0, 5, 10, 20, 30 and 60 days after injection. The results disclosed that most of the estradiol derivatives evaluated exhibited a long-acting estrogenic action. However, the monoesters at C-17 showed longer effects that monoesters at C-3, while the estradiol diesters exhibited the shortest effects. In addition as shown by its low serum levels, all estradiol esters with unsaturated fatty acids show a decreased E2 absorption. The overall results indicated that esterification of E2 with long chain fatty acids provided long-acting properties to it, being higher with C-17 esters. Whether some of these compounds could be employed in substitutive endocrine therapy remains to be established.
Vazquez-Alcantara
M A
MA
Departamento de Bioquimica, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, D.F.
Menjivar
M
M
Garcia
G A
GA
Díaz-Zagoya
J C
JC
Garza-Flores
J
J
D000818:Animals; D004952:Esters / Q000494:pharmacology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D010052:Ovariectomy; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014599:Uterus / Q000187:drug effects; D014621:Vagina / Q000187:drug effects
D004952:Esters; D045166:Estradiol Congeners; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone