John P Hearn and Georgina E Webley, Reproductive Health Research Programme (HRP), World Health Organisation, Geneva, Switzerland
The immunological manipulation of endocrine and allied reproductive regulatory systems provides us with an example of how both our basic knowledge and its applied dimensions have progressed through the interdisciplinary catalysis of immunology and reproductive biology. Over the first 70 years of the twentieth century, the complex feedback interactions between gonadotropins and steroids were described, resulting, for example, in new approaches to infertility (gonadotropin releasing hormone, GnRH), fertility control (the contraceptive pill) and the management of domesticated farm stock (progesterone sponges, prostaglandins). By the early 1970s, pure preparations of most of the generic hormones were available and their mechanisms of action had been tested through immunological neutralization. The discovery by Canfield and Pierce in 1971 of the sub-unit structures of the gonadotropins explained why previous attempts to immunize against the entire hormones - luteinizing hormone (LH), follicle-stimulating hormone (FSH), chorionic gonadotropin (CG) - resulted in cross-reactions between these and thyroid-stimulating hormone. It also allowed progression from crude immunizations to the development of specific epitope, anti-idiotypic and sequenced subfraction antibodies, now progressing to the sequencing of the key genes and prohormones. The discovery that potential 'vaccines' against self antigens could be achieved, through conjugation with nonself antigens, such as tetanus toxoid, opened new avenues for the development of immunological fertility regulation. In addition, a range of new immunological probes to study gamete maturation, receptor function, sperm and egg surface antigens, embryonic cell signal transduction, trophoblast and placental antigens, and the embryo-maternal dialog at implantation have become available, together with some advances in adjuvant technology that reduce the trauma of immunization with Freund's adjuvant. Species differences in the sequences and antigenicity of gonadotropins, or the differing emphasis in biological actions between related groups of progestagens, androgens or estrogens in various species, still hinders the easy extrapolation of results between species. However, similarities between the endocrine and immunological characteristics of the fetal allograft with those of certain carcinomas has allowed some shared approaches to diagnosis and monitoring, for example with CG in pregnancy, choriocarcinoma or teratocarcinoma.
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