Endocrine aspects of human uterine sarcoma: a preliminary study.
The biologic effect of estrogen and progesterone in human uterine sarcoma is poorly understood in comparison to that of endometrial adenocarcinoma. In an attempt to elucidate the endocrine status of these tumors, we have investigated the ability of these tumors to synthesize estrogen by measuring the aromatase activity and studied the effect of aromatase inhibitors on the activity. In addition, the effect of estrogen and progesterone on aromatase activity and the growth pattern of these tumors were studied in cell culture and athymic mice systems. Aromatase activities in eight uterine sarcomas ranged from 0.7 to 37 fmol/hr X mg protein, which were within the range or higher than the activity found in normal proliferative endometrium (0.5 to 3 fmol/hr X mg of protein, means = 1.6, n = 10). These results indicate that uterine sarcomas are capable of producing estrogen. However, the enzyme activity showed no correlation with the morphology of tumors or the age of patients. Results from the kinetic studies of aromatase activity in one of the uterine sarcomas indicated that 19-nortestosterone, testolactone, and aminoglutethimide (the most effective one) inhibited aromatase activity. In addition, induction of aromatase activity in two uterine sarcomas was investigated in cell cultures. Progesterone caused an eightfold increase in activity in a sarcoma that was estrogen and progesterone receptor positive but had no effect in a tumor that was estrogen and progesterone receptor negative. The growth rate of two estrogen/progesterone receptor-negative uterine sarcomas was studied in cell culture and in athymic mice. Progestin, but not estrogen, reduced the growth rate in both systems; 30 nmol/L of estrogen had no effect on the growth rate. In summary, we have found that human uterine sarcoma is able to synthesize estrogen. Progesterone is able to induce the aromatase activity in estrogen/progesterone receptor-positive tumors, and progesterone also suppresses the tumor growth rate in estrogen/progesterone receptor-negative tumors. These results suggest that a select group of uterine sarcomas is sensitive to steroid hormone and that progesterone may be potentially beneficial for therapeutic treatment of select uterine sarcomas.
D000328:Adult; D000368:Aged; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009277:Nandrolone / Q000494:pharmacology; D009368:Neoplasm Transplantation; D011374:Progesterone / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012509:Sarcoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000616:Aminoglutethimide; D011374:Progesterone; D004958:Estradiol; D009277:Nandrolone; D017258:Medroxyprogesterone Acetate; D001141:Aromatase; D008525:Medroxyprogesterone