DELAY OF IMPLANTATION IN INTACT RATS TREATED WITH PROGESTINS

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Abstract
Compounds were administered daily by the subcutaneous route to pregnant rats from day 1 of pregnancy (the day of finding sperm) to day 8, and 1 [mu]g oestrone combined with 4000 [mu]g progesterone from day 9-21. Animals were checked for implantation sites by laparotomy on day 8 and again on day 15, if no sites were visible on the 8th day. Autopsy was performed on day 22 of pregnancy. Delay of nidation was produced with 6a-methylprogesterone (ED50 = 3000 [mu]g), 17[alpha]-acetoyx-6[alpha] -methylprogesterone (ED50 = 720 [mu]g) and its 21-fluoro (ED50 = 470 [mu]g) and 6-dehydro-21-fluoro (ED50 = 3500 [mu]g) derivatives, and 17[mu]-ethyl-19-nortestosterone (ED50 = 3200 [mu]g), but not with progesterone, 17[alpha]-acetoxyprogesterone, or 17[alpha]-acetoxy-6-dehydro-6-methylprogesterone. Foetal body weights in not delayed groups given 17[alpha]-acetoxy-6[alpha]-methylprogesterone (>500 [mu]g) and its 6-dehydro-21-fluoro analogue were much smaller than in control rats indicating the occurrence of additional partial delays of short duration undetectable by laparotomy on the 8th day. The number of implantation sites was reduced with 17[alpha]-ethyl-19-nortestosterone (>500 [mu]g/day) but not with any of the other compounds. The implantation rate achieved with a particular dose of a compound was similar in groups in which implantation was delayed ("delayed") and not delayed ( nondelayed). In another study implantation occurred spontaneously within 8 days after cessation of all steroid treatments. The data are discussed in terms of a possible mechanism of action involving the development of an oestrogen deficiency in the animal resulting indirectly from the suppression of production or release of gonadotrophin from the pituitary gland.