GREGORY PINCUS 
uterine response to the progestin. Recently, Dr. Miyake, Miss 
Merrill, Miss Longo and I took up this question again and 
developed another assay method for progesterone involving 
measurement of an enzyme in the endometrium. Using this 
enzyme method we were able to measure the antagonistic, or 
antiprogestational, effect of the oestrogens, and were thus able 
to examine a large number of steroids as possible antiprogestins. 
We found a limited number ofsignificantly active compounds’. 
These fell into two categories: (1) derivatives or close chemical 
relatives of the steroidal oestrogens and (2) certain other steroids 
without oestrogenic activity. The first group appear to act as 
physiological antagonists and the second as competitive anta- 
gonists. Among the compounds of the second group, several 
appear to have only this progesterone-inhibiting effect and no 
other hormonal activity, in contrast to the oestrogen derivatives, 
which possess the numerous functions associated with oestrogen 
activity. 
On the assumption that antiprogestins should act to inhibit 
ovum growth and implantation, Dr. U. Banik and I have 
examined the effects of a number of these compounds adminis- 
tered to rats and mice carrying fertilized ova. Females were 
caged with males overnight and examined the next morning 
for the presence of vaginal plugs and sperm to ensure that 
copulation had taken place. Administration of the antipro- 
gestins was begun 24 hours later (called day 1 of pregnancy) 
and then on two subsequent days. Most of the compounds tested 
did indeed inhibit implantation in both rats and mice. Some 
of the others appeared to be effective in one species only, where- 
as some failed to inhibit implantation despite administration at 
comparable dose levels. In addition, it should be noted that 
antiprogestational activity in the rabbit is not paralleled by 
implantation inhibition in rats and mice. We have observed 
too that among the active compounds doses that are less than 
100 per cent effective in preventing implantation may still 
significantly reduce the number of uterine implantations. 
Dr. Banik and I thought that since implantation occurs by 
the eighth day its inhibition could be more easily accomplished 
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