Inhibition of masculine differentiation in male offspring of rabbits actively immunised against testosterone before pregnancy

Abstract

ACTIVE immunisation of male rabbits with testosterone–protein conjugates results in the production of antibodies capable of neutralising the biologic activity of endogenous testosterone¹. Due to the reduction of free, biologically active testosterone caused by almost total binding to antibodies the entry of this hormone into the target cells is inhibited, the metabolic clearance rate is decreased, the negative feedback to the hypothalamus is interrupted and pituitary gonadotropin release is increased. Thus, in spite of enormously elevated total plasma testosterone concentrations, atrophy of the prostate, paraprostate and seminal vesicles can be observed in suitably immunised male rabbits. In female rats actively immunised against testosterone Hillier et al.² also observed—despite significantly elevated total plasma testosterone concentrations—a considerable reduction of the free testosterone fraction and an elevation of FSH. Histological examination of these animals revealed development of polycystic ovaries, similar to those seen in the Stein–Leventhal syndrome in humans. These reports prompted us to study whether it is possible to fertilise female rabbits after active immunisation against testosterone, and whether in pregnancy the antibodies pass through the placenta in sufficient concentrations to neutralise the biologic activity of testosterone secreted by the foetal testes, thus selectively inhibiting the testosterone-dependent steps of male sex differentiation. We found inhibition of masculine differentiation in offspring of rabbits actively immunised against testosterone before pregnancy.