Progestins and antiprogestins: a review of their role in medicine and bioassays used in their development

By Bigsby, R.M.

The physiological role of ovarian progesterone in reproduction and the medical uses of synthetic progestins and antiprogestins are briefly reviewed. Although a number of progestins are in wide use, the search continues for better analogues that display fewer of the unwanted effects of the present compounds. The one antiprogestin approved for human use to date, RU486, exhibits considerable antiglucocortoid activity. The classical bioassays currently in use for the development of these steroid analogues depend upon in vivo progestin effects. However, progestins induce measurable responses in several cell culture systems that could be used as alternative bioassays. Rabbit uterine stromal cells in primary culture are especially suitable for such use. Addition of progesterone to these cultures stimulates synthesis of a 42 kilodalton (42kD) protein that appears in the medium. The 42kD protein response is specific for a progesterone receptor-mediated event and it can be blocked by known progestins. Using this culture system as a bioassay, one rabbit yields enough cells to measure the effect of 30 test doses in triplicate. Thus, a culture system is described that could substitute for current in vivo bioassays. This culture bioassay would allow large scale screening for potential progestin or antiprogestin activity.