Biological mimicry of gonadotropin action by antiidiotypic antibodies to luteinizing hormone: characterization and biological properties.
High affinity polyclonal rabbit antibodies to ovine (o) pituitary LH [anti-oLH-immunoglobulin G (IgG) Ab1] were used to immunize young Southdown lambs. Their serum samples as well as those from controls receiving normal rabbit IgG were studied for the presence of anti-Ab1 antibodies. In RIAs using [125I]oLH and affinity-purified Ab1, sera from experimental sheep showed high activity, as expressed in oLH equivalents. These sera also showed ability to compete with [125I]oLH for binding to receptor on pig ovarian and testicular membranes. The antiidiotypic antibodies (Ab2) in experimental sheep sera were purified by successive affinity chromatography on immobilized rabbit normal IgG and immobilized oLH-IgG columns. Ab2-IgG eluted from the latter mimicked oLH in RIAs and RRAs. These purified Ab2 antibodies were also of a stimulatory type, because they elicited progesterone production in rat granulosa cells and collagenase-dispersed rat Leydig cells. This stimulatory action was counteracted by coincubation with anti-oLH-IgG, which would also terminate (oLH) hormone action in a similar manner. The Ab2 antibodies had no effect on oFSH RIA or on the binding of [125I]oFSH to pig ovarian receptors, indicating specificity with respect to LH antigenic structure and function. As can be expected from the choice of the immunogen (polyclonal anti-oLH-IgG), only a small percentage of the true Ab2 population could display biological mimicry of the original antigen (oLH). Their presence in circulation during 6-8 months had no effect on testicular size or body growth. The formation of Ab2 antibodies to rabbit anti-oLH-IgG was also demonstrated in male rats, but these were not purified. In this instance also there was no effect on testicular weight after 6 months of immunization. These results show the feasibility of producing antiidiotypic antibodies that stimulate gonadal function in a manner much like the pituitary gonadotropin (oLH).
Sairam
M R
MR
Reproduction Research Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Bhargavi
G N
GN
Downey
B R
BR
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000302:isolation & purification; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000302:isolation & purification; D007700:Kinetics; D007986:Luteinizing Hormone / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011974:Receptors, LH / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012756:Sheep; D013552:Swine; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D011974:Receptors, LH; D011374:Progesterone; D007986:Luteinizing Hormone