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Immunization of female rats with crude preparations of delta 5-3 beta-hydroxysteroid dehydrogenase combined with complete Freund's adjuvant resulted in suppression of the endogenous enzyme activity in the ovarian interstitial tissue and the corpora lutea. As a result, estrous cyclicity, nidation, or maintenance of pregnancy was adversely affected in proportion to the level of the antibody to the enzyme following the series of immunizations. On the basis of the biologic response, it can be assumed that progesterone synthesis was reduced as a result of neutralization of enzyme action in the ovary by the formation of antibodies to the delta 5-3 beta-hydroxysteroid dehydrogenase. Further studies are required to verify this assumption.

Rhesus monkeys were immunized against the beta subunit of sheep luteinizing hormone (LH; oLHbeta) as an animal model for immunity against chorionic gonadotropin for fertility control. oLHbeta has been demonstrated to cross-react with rhesus chorionic gonadotropin (rhCG) but not rhesus LH. 13 multiparous monkeys received 50 mcg oLHbeta in complete Freund's reagent at 4 sc sites, repeated in 3 weeks and occasionally afterward. All developed circulating antibodies that bound hCG and oLH. RhCG was assayed in a competitive ligand binding assay using receptors from rat testis. Monkey antiserum bound hCG, 12.5% of which was displaced by 100 mcg rhLH. Antisera from 2 monkeys neutralized rhCG bioassayed in the immature rat uterine weight assay in a dose-related manner. After 2 immunizations 11 of the 13 macaques has regulat ovulatory menstrual cycles. 10 of them were mated 28 times, 1-5 each, at ovulation. There was only 1 pregnancy after 1 year in a monkey whose antibody titer had declined. In comparison, 5 of 10 controls, mated once each at ovulation, became pregnant. The mechanism by which immunization prevented pregnancy is unknown. Furthermore, use of a heterologous antigen in lieu of rhCG whose structure is unknown, may have minimized possible adverse effects.

The effect of antibovine luteinizing hormone (LH) serum on the Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-OHSDH) and the 20α-hydroxysteroid dehydrogenase (20α-OHSDH) activity in the ovaries of pregnant rats was studied and correlated with changes in the state of pregnancy. The apparent neutralization of LH during days 7–11 of pregnancy resulted in termination of the pregnancy by fetal reabsorption and the reappearance of strong 20a-OHSDH activity in the corpora lutea. Such an enzymatic reaction is not normally demonstrable at this time. Concomitantly, the Δ6-3β-OHSDH activity decreased below the normal expected values. Concurrent administration of progesterone prevented the effects of the anti-LH treatment. Neutralization of LH from the 12th to the 16th day of pregnancy led to similar results if the antiserum treatment was initiated on the morning of the 12th day of pregnancy. Later treatment, particularly from days 14–18, failed to affect either the normal development of the pregnancy or the normal patter...

Antisera to the conjugate of beta-human chorionic gonadotropin and tetanus toxoid (βhCG-TT) generated in rabbits receiving TT carrier preimmunization were characterized and compared with antisera from rabbits receiving the conjugate without preimmunization. Double immunodiffusion and immunoelectrophoresis were used to identify individual antisera components to the conjugate and its substructures. 125IhCG radioimmunoassay indicated similar antibody titers (P = 0.447) regardless of whether the rabbits were preimmunized with TT. However, bioneutralization of native hCG as measured by inhibition of prepubertal rat uterine weight increase was significantly more effective (P = 0.025) with antisera from rabbits which received carrier presensitization. These results demonstrate that carrier preimmunization provides a method for increasing the efficacy of neutralizing antibody produced against haptenic βhCG.

Immunologic techniques have proven to be useful tools in characterizing the action of pituitary protein hormones on the target organs. Specifically, an antibody to luteinizing hormone can prevent ovulation, delay implantation, or cause fetal resorption depending on the time of administration of the antiserum to female rats. The immunologic interference with ovarian function appears to be associated with the steroidogenesis process during early pregnancy, and with fetal placental function during mid pregnancy in the rat. Progesterone synthesis is diminished, probably by the prevention of luteinizing hormone from stimulating the Δ5Β hydroxysteroid dehadrogenase within the interstitial tissue of the ovary. In later pregnancy, the antibody combines with specific cells within the placenta, thereby eliminating any placental influence on the ovarian steroidogenic process.

To histologically and biologically assess the impairment of testicular function after active immunization with LH, adult male rats (49) and rabbits (9) were actively immunized with bovine LH and then compared with saline-injected controls. When the measured antibody titer was high, the mating behavior of the males was altered. The males mated only 41.8% of the time when exposed to cycling females. The control group mated 90% of the time. Testicular weights were unchanged but the seminiferous tubules of the experimental group showed vacuolation in the Sertoli cells with some of the spermatids being multinucleated. Passive immunization of rats with anti-LH sera diminished mating capacity to a greater extent than active immunization. Immunization of rabbits led to a rapid decrease in libido. Uniform interruption of spermatogenesis was noted along with a loss of testicular weight of immunized rabbits. The probable mechanism of the LH inhibition of spermatogenesis is the interference with androgen production in the interstitial tissue.