title: Binding of estradiol-17-fatty acid esters to plasma proteins.
abstract: The C-17 fatty acid esters of estradiol are a unique family of long-acting estrogens that circulate in blood. The unusual duration of the estrogenic action of these esters has been shown previously to correlate with their very slow rate of metabolism. However, in striking contrast to their slow rate of metabolism, the clearance of these esters from blood is relatively rapid, not very different from that of estradiol (E2). Studies on the effect of the size of the carboxylic acid moiety on the rates of both metabolism and clearance have suggested that an active process might be involved in the cellular uptake of these circulating esters, and this, in turn, raised the question of how E2-fatty acid esters are transported in blood. The binding of representative E2-17-fatty acid esters to both human and rat plasma proteins known to bind either E2 or fatty acids was investigated. As expected, both E2 and 5 alpha-dihydrotestosterone bound to human sex hormone-binding globulin, whereas none of the E2 esters bound to this human plasma protein. Similarly, E2 bound to rat alpha-fetoprotein (AFP) and unsaturated fatty acids bound to both human and rat AFP, but none of the E2 esters bound to AFP of either species. These steroid esters bind to lipoproteins. Over 85% of a representative ester, E2-17-stearate, partitioned in the lipoprotein fractions of both human and rat serum, while the synthetic short chain ester, E2-17 beta-acetate, like E2 itself, partitioned predominantly in the nonlipoprotein fraction of blood. These results demonstrate the unusual binding of a family of steroid hormones to plasma lipoproteins and open the possibility that they are transported into target cells through the mediation of lipoprotein receptors.
mesh_terms: D000818:Animals; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000097:blood; D004952:Esters; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D004952:Esters; D005227:Fatty Acids; D008074:Lipoproteins; D012738:Sex Hormone-Binding Globulin; D000509:alpha-Fetoproteins; D013196:Dihydrotestosterone; D004958:Estradiol; C047073:estradiol-17-arachidonate; C045404:estradiol-17-stearate