Estrogen Antagonisms: Inhibition of Estrone-Induced Uterine Growth by Testosterone Propionate, Progesterone and 17-ethyl-19-nortestosterone

Abstract

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.

Interactions Between Oestradiol and Progestogens in the Uterus of the Mouse

“…In the rabbit it inhibits the effects of oestrogen on uterine motility (Reynolds & Allen, 1932) and reverses oestrogenic inhibition of progestational proliferation (Robson, 1936). Similar results have been obtained in the baboon (Gillman & Stein, 1939), while in the mouse the injection of progesterone prevents uterine weight increase under the influence of oestrogen (Edgren & Calhoun, 19576). Early attempts to prevent the anti-fertility action of oestrogens with progesterone in rabbits (D'Amour & Gustavson, 1934) and mice (Courrier & Friere, 1953) were unsuccessful.…”

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dietary phytoestrogen analyses.

“…In contrast, the estimation of TGE rests on a) the largely untested assumption of direct additivity between weak ER agonists in vivo, and b) an assessment of various literature data to derive the potency of various phytoestrogens. The tissue specificity of ER ligands (Shang and Brown 2002) and the interaction studies of Edgren and Calhoun (1957, 1960, 1961 suggest both caution and the need for robust experimental data.…”

“…The second qualification arises from data generated from the co-administration of several estrogenic compounds in the uterotrophic bioassay (Edgren and Calhoun 1957, 1960, 1961. These results question direct additivity and linearity of the equivalency assumption across a range of doses, suggesting some degree of additivity in the lower region of the dose-response curve and antagonistic activity in the higher region of the dose-response curve.…”

Studies on the Interactions of Oestriol and Progesterone

“…They found oestriol to be about as potent as oestrone, oestradiol-17ß or stilboestrol in this test, despite the fact that oestriol is usually considered to be a weak oestrogen when given systemically (Merrill, 1958). Merrill (1958) The effects of progesterone upon oestriol-induced uterine growth have been evaluated by methods described previously (Edgren & Calhoun, 1957b). Briefly, the compounds to be studied were administered subcutaneously, either individually or in combination, in 0-3 ml of corn oil.…”