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-E2 15 plus oestrogen (E2) potentiated the specific activity of the brain type creatine kinase (CK) response to E2 in the rat tissues or skeletal cells. The enhancing CK response of anti E2 15 plus E2 was time- and dose-dependent in the uterus, thymus, epiphysis and diaphysis of ovariectomized female rats. In the pituitary, on the other hand, anti-E2 15 blocked the stimulatory CK response to E2. Two other high affinity anti-E2 antibodies, clones 8D9 and 11B6, had no effect in augmenting the response of CK to E2 in rat tissues. Moreover, the enhancing CK response in rat tissues was specific to anti-E2 15 plus E2 since the intact anti-E2 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-E2 15 abolished the CK response to E2 in rat tissues and not to anti-E2 15 plus E2 whereas tamoxifen completely blocked the CK response to anti E2 plus E2. Anti E2 15 may therefore serve as a specific carrier in delivering E2 to oestrogen sensitive rat tissues or cells containing functional oestrogen receptors and thereby increasing the magnitude of E2 effects in vivo and in vitro.
Sömjen
D
D
Endocrine Unit, Tel Aviv Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Israel.
Amir-Zaltsman
Y
Y
Mor
G
G
Gayer
B
B
Lichter
S
S
Nevo
N
N
Kohen
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000276:immunology; D004958:Estradiol / Q000276:immunology* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000276:immunology / Q000494:pharmacology; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010052:Ovariectomy; D013629:Tamoxifen / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004965:Estrogen Antagonists; D007140:Immunoglobulin Fab Fragments; D013629:Tamoxifen; D004958:Estradiol; D003402:Creatine Kinase