A bioassay for the evaluation of antiproliferative potencies of progesterone antagonists.
A bioassay which allows quantification of the antiproliferative potency of progesterone antagonists on the mammary gland was developed. For this purpose, ovariectomized rats were substituted with oestrone and progesterone and a further group simultaneously treated with the progesterone antagonists Mifepristone (= RU 38.468), Onapristone (= ZK 98.299), or ZK 112.993 (Schering AG, Berlin). A morphometric analysis of the tubulo-alveolar buds in the inguinal mammary glands revealed a dramatic antiproliferative effect of the progesterone antagonists after as little as 3 days of treatment. Several less specific mammary gland growth parameters (weight, DNA- and RNA-content) proved to be less sensitive. This bioassay measures the potency of progesterone antagonists to competitively antagonize the specific effects of progesterone on the target organ mammary gland. Further advantages of this bioassay are the use of a hormonally standardized biological system, the quantitative results, the small amount of test compound necessary, as well as the substitution with progesterone and oestrone since the antiproliferative potency of progesterone antagonists on experimental hormone dependent mammary carcinomas is most potently displayed in ovariectomized animals substituted with both sex hormones.
Michna
H
H
Research Laboratories of Schering Berlin, Germany.
Nishino
Y
Y
Schneider
M R
MR
Louton
T
T
el Etreby
M F
MF
D000818:Animals; D004247:DNA / Q000032:analysis; D005260:Female; D006067:Gonanes / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects*; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009929:Organ Size; D011374:Progesterone / Q000037:antagonists & inhibitors*; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D006067:Gonanes; C064879:ZK 112993; D015735:Mifepristone; D011374:Progesterone; D012313:RNA; D004247:DNA; C053238:onapristone