Anti-idiotypic antibody as an oestrogen mimetic in vivo: Stimulation of creatine kinase specific activity in rat animal models

Previous studies indicated that the anti-idiotypic antibody (clone 1D(5)) significantly increased the specific activity of creatine kinase (CK) activity in the rat uterus, and in vitro in skeletal cells capable of responding to oestradiol (E(2)), suggesting that the antibody has oestrogenic-like activity. Moreover, the F(ab')(2) dimer of clone 1D(5) acted like an antagonist and completely inhibited the increase in CK specific activity by either E(2) or clone 1D(5) in these skeletal cells. In the present study, we examined the in vivo effects of clone 1D(5) and its proteolytic fragment, the F(ab')(2) dimer, E(2) and dihydrotestosterone (DHT) on CK specific activity in the epiphyseal cartilage, diaphyseal bone, uterus, prostate, thymus and pituitary of immature or gonadectomized female and male rat animal models. In the intact immature animals, clone 1D(5) caused an increase in CK in all organs of the female except in the pituitary. In the diaphyseal bone and prostate of male rats there was no stimulation by 1D(5). The CK response in the uterus, epiphysis, and diaphysis of immature female rats was dose-dependent and was blocked by either the antioestrogen tamoxifen or the F(ab')(2) dimer of clone 1D(5). E(2), DHT, as well as clone 1D(5), stimulated CK specific activity in both the diaphysis and epiphysis of ovariectomized female and castrated male rats, whereas sex specificity in the CK response was observed also in the uterus and the prostate of gonadectomized animals. Collectively, these results suggest that, as in cell culture, an intact antibody is necessary for the observed stimulation of CK specific activity and the F(ab')(2) dimer can act as an antagonist. Furthermore, the observed biological effects of clone 1D(5) which are absolutely parallel to E(2), imply that the anti-idiotypic antibody is able to penetrate the cell and reach the nuclear oestrogen receptor and transduces a signal to the nucleus, by as yet uncharacterized mechanisms.