A wide variety of the metabolic processes in the ovary are controlled, activated or enhanced by the pituitary luteinizing hormone (LH). These include follicular development, oocyte maturation, ovulation, formation and maintenance of the corpus luteum, as well as, steroid production. LH presumably regulates these events through the interaction of a specific membrane bound receptor (LHR). Since LH plays such a critical role in the regulation of ovarian function, interventions with its action will most likely effect fecundity and provide new opportunities for developing safe and efficacious techniques for human contraception. In this study we plan to determine if passive immunization with LHR mAB will produce a state of infertility without complicating physical or psychological side effects. We have recently purified the LHR from porcine ovaries by affinity gel chromatography to near homogeneity and we have produced a polyclonal antibody in the mouse against this receptor. In this grant proposal we plan to (1) generate mouse monoclonal antibody (mAB) against the LHR' (2) screen the mAB(s) for those that can interfere with LH binding to LHR and (3) study the effects of mAB(s) on ovarian cells in vitro and in vivo systems. To test the contraceptive potential of mAB(s), three different animals will be passively immunized with this mAB(s). To reduce the possibility of an immunogenic response of the animal to the injected mAB(s), the mAB(s) will be treated with pepsin which alters the antibody making it less immunogenic but does not alter its biological potency. The effects of the mAB(s) on the reproductive system on immunized animals will be examined by monitoring steroid production, morphological changes and the ability of the animals to conceive.
| Nau, E A; Epsaro, E M; Scherer, M S et al. (1996) Monoclonal antibodies specific for the binding site on the LH receptor alter progesterone production in cultured granulosa cells. J Endocrinol 150:9-16 |
