Long-acting estrogenic responses of estradiol fatty acid esters

https://doi.org/10.1016/0022-4731(89)90417-2Get rights and content

Abstract

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 μmol of each ester and compared with those observed with 17β-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17β-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.

References (18)

There are more references available in the full text version of this article.

Cited by (24)

  • Fatty acid esters of steroids: Synthesis and metabolism in lipoproteins and adipose tissue

    2011, Journal of Steroid Biochemistry and Molecular Biology
    Citation Excerpt :

    The authors speculated that clofibrate might have potentiated the estrogenic effect of estradiol on the mammary gland by enhancing the hydrolysis of estradiol fatty acid esters in the surrounding fatty tissues [30]. Early studies have indicated that, when injected parenterally, estradiol 17-esters are metabolized more slowly than nonesterified estradiol leading to an increased duration of the estrogenic signal [31–33]. More recently, Paris et al. observed that also orally administered estradiol 17-stearate was more slowly metabolized and induced a stronger uterotrophic effect than unesterified estradiol in juvenile female rats [34].

  • Evolution of oestrogen functions in vertebrates

    2002, Journal of Steroid Biochemistry and Molecular Biology
View all citing articles on Scopus
View full text