A monoclonal antibody to oestradiol potentiates the stimulation of the specific activity of the brain type creatine kinase by oestrogen in vivo and in vitro

We described previously the in vivo immunoneutralization effects of a high affinity anti-oestradiol antibody clone 15 in blocking ovulation and synaptic remodeling in cycling female rats. In the present study we report the enhancing effects of this antibody. Treatment of ovariectomized female rats or female derived skeletal cell cultures in vitro with anti-E 2 15 plus oestrogen (E 2) potentiated the specific activity of the brain type creatine kinase (CK) response to E 2 in the rat tissues or skeletal cells. The enhancing CK response of anti E 2 15 plus E 2 was time- and dose-dependent in the uterus, thymus, epiphysis and diaphysis of ovariectomized female rats. In the pituitary, on the other hand, anti-E 2 15 blocked the stimulatory CK response to E 2. Two other high affinity anti-E 2 antibodies, clones 8D 9 and 11B 6, had no effect in augmenting the response of CK to E 2 in rat tissues. Moreover, the enhancing CK response in rat tissues was specific to anti-E 2 15 plus E 2 since the intact anti-E 2 in the presence of other oestrogen mimetics, such as oestriol or stilbestrol or tamoxifen did not potentiate the CK response in rat tissues. In this model system the Fab′ monomer of anti-E 2 15 abolished the CK response to E 2 in rat tissues and not to anti-E 2 15 plus E 2 whereas tamoxifen completely blocked the CK response to anti E 2 plus E 2. Anti E 2 15 may therefore serve as a specific carrier in delivering E 2 to oestrogen sensitive rat tissues or cells containing functional oestrogen receptors and thereby increasing the magnitude of E 2 effects in vivo and in vitro.