Abstract

Evidence is present that alpha-fetoprotein (AFP), a serum globulin, accounts mainly, if not entirely, for the high estrogen-binding properties of uterine cytosols from immature rats. By the use of specific immunoadsorbents to AFP and by competitive assays with unlabeled steroids and pure AFP, it has been demonstrated that in hypotonic cytosols AFP is present partly as free protein with a sedimentation coefficient of about 4-5 S and partly in association with some intracellular constituent(s) to form an 8S estrogen-binding entity. The AFP leads to 8S transformation results in a loss of antigenic reactivity to antibodies against AFP and a significant change in binding specificity. This change in binding specificity is manifested by an increase in binding affinity for estradiol, estriol, diethylstillbestrol, and nafoxidine ( a non-steroidal anti-estrogen), and by a concomitant decrease in estrone binding. Both the antigenic and binding properties of native AFP are recovered after dissociation of the 8S complex in 0.4 M KC1. An AFP-mediated mechanism of early intracellular events associated with estrogen entry in target cells is suggested and discussed with regard to current views on steroid action.