Progesterone withdrawal induced by ICI 81008 in pregnant rats

Of a total of 343 pregnant rats treated with the prostaglandin F2 analogue ICI 81008, 137 aborted, while 83 had reduced and 123 intact litter. These biological variations depended primarily on the gestational timing of treatment and on the dose and route of administration of this synthetic PG. In comparison with the 107 controls, all experimental rats which aborted had a drastic reduction in plasma progesterone levels which was highly significant (P<0.001) until day 18. In contrast, those animals which escaped suboptimal ICI 81008 treatment with a partly resorbed litter, only had a moderate reduction in progesterone which was statistically significant (P<0.01) until day 16 when the levels of this steroid normally begin to decrease. Ineffective treatment did not affect progesterone levels and intact pregnancy. In contrast to progesterone, there was no correlation between plasma estradiol-17β levels and the consequences of ICI 81008 treatment.

ICI 81008 was most effective between the 6th and 12th days of gestation, when plasma progesterone in the normal controls showed a nadir. Effective treatment reduced plasma progesterone within 6 hours. Evidently the pharmacologically provoked endocrine imbalance precedes the cessation of characteristic gestational weight gain, uterine bleeding and abortion which only manifest 24 to 48 hours after treatment.