Differential Uterine Responsivity to Diethyistilbestrol: Apparent Bases for Contrasting Estrogenic Potency1

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Abstract
The effects of the naturally occurring steroid estradiol-17.beta. (E) and the synthetic, nonsteroidal estrogen diethylstilbestrol (DES) upon uterine H2O inhibition, long-term growth, contractile tension development and actomyosin production were monitored in relation to the temporal pattern of the nuclear retention of the receptor-estrogen complex (REC) for each hormone. The relative potency of the 2 to stimulate glucose oxidation was determined. True uterine growth was stimulated to a greater degree by DES than by E. The differential growth increase promoted by DES was 13.7 and 24.2% at a hormone dose of 0.1 and 1 .mu.g, respectively. The augmented growth response to DES was accompanied by a significantly (P < 0.05) elevated 6.5 h nuclear retention of the DES-REC compared with that for E at both hormone doses. The quantity of DES-REC still remaining in the nucleus at 12 h also tended to be greater than the nuclear retention of E. The same relationship between uterine growth and nuclear retention was observed in immature rats over a period of development in which the uterus was becoming more estrogen responsive and exhibiting an increasingly differential sensitivity to DES. The effect the 2 hormones had on development of uterine isometric tension and on nuclear retention of REC was qualitatively and quantitatively similar to the uterotrophic response. The contractile response to DES was associated with significantly (P < 0.05) greater actomyosin production. No relationship existed between estrogen-stimulated uterine fluid uptake and nuclear retention of REC. Although DES was much less potent in this parameter, the temporal pattern and quantity of REC occupying the nucleus after DES treatment was inconsistent with this observation. Water imbibition may not be obligatorily coupled to nuclear REC interactions and may more accurately reflect differences in membrane interactions and/or uterine blood flow. E was the more potent hormone in stimulating glucose oxidation by the uterus. Only at a supramaximal dose did DES stimulate glucose utilization to an extent equivalent to that of E. Availability of oxidized coenzyme may be the limiting factor in the reduced sensitivity of uterine glucose oxidation to DES stimulation.