Session II: Hormonal dependency and sensitivity

Abstract

General interest was generated by the reported data correlating body weight in postmenopausal women, both with the incidence of endometrial cancer (Dr. MacMahon) and with the rate of production of estrogens from circulating adrenal androgens (Dr. Siiteri). This convergence of epidemiologic and biochemical studies stimulated discussions. Dr. Wynder brought up the possibility that nutritional factors related to obesity may influence the conversion of androstenedione to estrone, and Dr. Velios suggested that various types of adipose tissue might differ in their aromatase activity. The need for more data on the extent of aromatization in obese children and young women was emphasized. It was evident from the presentations that the time is ripe for the study of hormonal factors involved in the development of endometrial cancer. Studies on the interaction of estradiol and progesterone with uteri of rodents, carried out by several groups during the last decade, have yielded concepts and methodology, mentioned by Dr. Gorski and by Dr. Wiest in their lectures, which can now be applied to the study of human endometrium. Comparative biochemical studies can be designed to take advantage of the availability of various types of normal and abnormal tissue, including early, mid, and late proliferative and secretory normal endometrium, postmenopausal, cystic, and adenomatous hyperplastic tissue, as well as differentiated and undifferentiated carcinoma. Dr. King and Dr. Taylor reported in the discussion period that they have observed an increase in the level of total estradiol receptors during the proliferative phase of the menstrual cycle followed by a decrease during the secretory phase. They interpreted the results to indicate that estradiol induces the formation of its own receptor. Similar changes were seen in Fallopian tubes. Low levels of estradiol receptors in cystic hyperplasia were found by Drs. King and Taylor, who indicated that these results do not support the concept of an increased organ sensitivity in cystic hyperplasia. Dr. Siiteri’s suggestion that estrone and estradiol might have a somewhat different hormonal effect on the endometrium was further discussed. This suggestion is of considerable interest since estrone rather than estradiol is the estrogen produced endogenously in postmenopausal women. Various discussants emphasized the need for accurate measurements of the levels of these estrogens in tissue, including endometrial and breast carcinoma. It was pointed out, however, that different relative concentrations of estrone and es-