Summary. The interactions of oestriol and progesterone were studied in a series of assays for oestrogenic and progestational activities, and the responses were compared with data on progesterone-oestrone combina¬ tions in the same tests. The vaginal effects of these two oestrogens do not seem to differ, whereas the interactions of oestriol and progesterone are quite different from the interactions of oestrone and progesterone when uterine end-points are considered. Since oestriol is the dominant aromatic steroid excreted during pregnancy and the luteal phase of the menstrual cycle, we feel that explanations for many unsolved problems of luteal-phase and pregnancy physiology may reside in these interactions.

ESTROGEN ANTAGONISTS 53 7 sera as described by Chang( 1!11) has not been a problem. We have found that only one of 23 human serum pools was toxic to FL cells.In preliminary experiments with FL and HeLa cells the FL cells have not produced tumors in treated rats using a technic3 in which HeLa cells produced significant tumors. More work is needed however before a conclusion can be established. Summary.A strain of human cells derived from a normal amniotic membrane has been cultivated in serial passage for 8 months in 30 transfers. This cell line was developed by trypsinization of the primary source and cultivated in a medium without embryo extract. The appearance of the cell has been epithelial-like a t all stages of cultivation. Growth characteristics in media containing human serum or animal sera are reported. The cell strain has been grown in large scale.

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175the chick comb in animals not treated with androgen were significnatly reduced by administration of this compound. A-norprogesterone is not androgenic, estrogenic, anti-estrogenic, progestational or an ti-proges ta tional under the experimental conditions described.

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Testosterone propionate (TP), at a high dose level, produces an increase in the uterine growth produced by oestrone, 17β-oestradiol or oestriol, also at high dose levels. When low doses of TP were added to relatively high doses of the oestrogens, they were found to be additive with oestriol, inactive with 17β-oestradiol and inhibitory only with oestrone. Although in the conditions of this test the major type of interaction between oestrogens and androgens is additive, an inhibitory component is sometimes present. This is in contrast to the findings of Velardo and our own mouse uterine growth studies in which inhibition was most obvious. This additive-inhibitory pattern of activities appears characteristic for mixtures of oestrogens and other steroids, which suggests a sort of buffering on the biological level.

Employing the vaginal smear as an index of effect, combinations of various estrogenic substances were tested for interaction. Studies were concentrated at the approximate 50% response level. In a single experiment ED50 doses of the two estrogens in pure form were administered to two groups of spayed rats and a third group was injected with a mixture of one-half of each ed50; in one experiment three intermediate doses were employed. In all of the studies a given proportion of the ED50 of one compound was replaced by the same proportion of the ED50 of the other without mensurable change in biological response. These data are interpreted as indicating simple additive relationships among the compounds tested. Pairs studied were: estradiol-17ß with estriol; and estrone in combination with estradiol-17ß, estriol, methallenestril (Vallestril) and stilbestrol. The additive relationships described here are of particular interest in view of literature reports that indicate an interference between certain pairs of these compounds when uterine growth rather than vaginal cornification was used as an index of activity. This target organ differentiation suggests that various end points of estrogenic action differ in their responses to varying hormonal balances.

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