Test Systems and their Use

The binding assays as well as the transactivation assays can be adapted to high-throughput screening formats, and allow a suitable determination of relative affinities and efficacies even for large libraries. 

Several animal models for the in vivo characterization of progestins were established at the beginning of the research in this field and are still established standards to evaluate the biological effects of new compounds [17]. 

Progesterone induces characteristic morphological changes of the endometrium after estrogen-induced proliferation of this tissue. This effect is the basis of the endometrium transformation assay, in which immature rabbits are primed with estradiol for several days and are subsequently treated with a progestin, either by oral application or by subcutaneous injection. The proliferating response of the uterus is examined by histological analysis and quantitated with the McPhail index on a scale from 1 to 4, with 4 as maximal effect. The assay is very sensitive and specific, even if the rabbit expresses only the B isoform of PR. 

For the maintenance of pregnancy in rodents the presence of progesterone produced by the corpus luteum is essential. Removal ofthe ovaries (ovariectomization) 

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