Active immunization of rabbits against progesterone: increase in hormone levels, and changes in metabolic clearance rates and in genital tract tissues

11 alpha-Hemisuccinyl progesterone was coupled to rabbit serum albumin and injected into intact male rabbits, and into intact ovariectomized female rabbits, for a period of 52 weeks. The ovariectomized females and the intact males showed better immune responses than the intact females. Specificity of the antisera was tested against both progesterone and the carrier protein, and against 19 other selected steroids. Antibody titres and serum levels of progesterone in all groups, and testosterones in the males, showed characteristic changes with a first maximum 12-18 weeks after the beginning of immunization, a decrease despite booster injections and a second increase after 35-40 weeks. Hormone levels were 5-12 times higher by the end of immunization than before. High antibody titres were correlated with decreased metabolic clearance rates for progesterone, reflecting the binding of the steroid to the antibody. Increased production rates of progesterone in the immunized females and of testosterone in the immunized males showed that the antibody-bound hormone was not available for feedback control. Absence of primordial follicles, hyperplasia of the Leydig cells, decreased spermatogenesis and involution of the seminal vesicle epithelium were interpreted as direct or indirect effects of the removal of free progesterone.