Estrogen-like activity of a subpopulation of natural antiestrogen receptor autoantibodies in man.
We recently reported that a subpopulation of immunoglobulin G (IgG) in man interacts with the hormone-binding site of estrogen receptors (ER), competes with [3H]estradiol (E2) uptake, and decreases effective ER concentrations in cell cultures. The present work further characterizes the immunological properties of these antibodies and defines their biological activity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques, enriched preparations of the natural anti-ER IgG subpopulation (IgGs) were found to specifically immunoprecipitate ER extracted from MCF-7 mammary carcinoma cells and to compete with [3H]tamoxifen-aziridine for ER binding. During 18-h incubations IgGs decreased [3H]E2 binding capacity of MCF-7 cells in a dose-dependent manner similar to E2. Like E2 but unlike antiestrogens, this biological effect corresponded to down-regulation of the receptor protein and depended on a mechanism specifically inhibited by actinomycin D. Moreover, IgGs antagonized the decrease of [3H]E2 binding capacity produced by the strong antiestrogen methyl-hydroxytamoxifen; this antagonism was additive to that of E2. On the other hand, IgGs like estrogens increased progesterone receptor concentrations and cathepsin D secretion. The biological activity of IgGs was neutralized by anti-IgG antibodies and by ICI 164,384, a "pure" steroid antagonist of E2, confirming that immunoglobulins G were responsible for this activity and acted at the E2-binding site. These observations indicate that some natural antibodies in man can function like potent estrogens on ER and mammary cells.
Borkowski
A
A
Laboratoire J.C. Heuson et Laboratoire d'Invetigation Clinique H.J. Tagnon, Institut Jules Bordet, Université Libre de Bruxelles, Belgium.
Gyling
M
M
Muquardt
C
C
Body
J J
JJ
Leclercq
G
G
D001323:Autoantibodies / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000276:immunology* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism; D014020:Tissue Extracts
D001323:Autoantibodies; D004967:Estrogens; D007074:Immunoglobulin G; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014020:Tissue Extracts; D013629:Tamoxifen; D004958:Estradiol; C031859:tamoxifen aziridine; C068941:2-methyl-4-hydroxytamoxifen