Effects of Natural Estrogens on L Strain Fibroblasts in Tissue Culture.

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Abstract
The effect of the three natural estrogens on L strain fibroblasts was studied. Estrone and 17[beta]-estradiol at a concentration of 3. 5 x 10-5 M in medium 199 supplemented with 0. 5[degree]/o bacto-peptone, completely inhibit the synthesis of deoxyribonucleic acid and protein in L strain fibroblasts. Estriol is not an inhibitor of L cell growth at the same concentration; in fact, DNA and protein synthesis occur at rates similar to control cultures. The extent of suppression of fibroblast growth can be related to the external concentration of estrone or estradiol below the level of 3. 5 x 10-5 M, and a direct relationship exists between the degree of inhibition and the external concentration to 10-7 M; below this level there is no inhibition. Morphological observation has shown that the initial reaction involves a reduced cell lar adhesiveness, which is followed by a rounding up of the cells in the population; these cells eventually fall off the glass surface. Swelling of the fibroblasts has not been observed. The reaction is reversible since cells that have fallen off the glass will spread and grow when placed into fresh medium devoid of these steroids. The suppression of macromolecular synthesis appears to be associated with the inability of glucose and amino acids to be transported into fibroblasts. The free amino acids that have accumulated into intra-cellular pools are retained. The magnitude of individual free amino acids in pools is comparable to control culture levels. Introduction of dialyzed horse serum into the medium results in resistance to the inhibitory action, and the extent of the reversal can be related to the serum concentration.