REMINE, W. H.; CHONG, G. C.; VAN HEERDEN, J. A.; SHEPS, S. G.; HARRISON, E. G. JR. Author Information
The aims of these studies were to determine if steriod metabolism differs in hormone-dependent and -independent tumors and to determine in these 2 types of tumors the effects of estradiol on tumor steroidogenesis especially 5alpha reduction. In this study 5 hormone-dependent rat mammary carcinomas and 2 hormone-independent tumors were compared. The patterns of steroid metabolism were determined by measuring the percentage incorporation of tritiate into the metabolites after purification and characterization. There was a wide variation in metabolism between individual tumors ranging from 20 to 90% transformation. The 2 hormone-independent tumors were among those with the highest metabolism. Addition of estradiol-17beta to the incubations produced variable results. The most common effect was inhibition on the level of testosterone metabolized. The 5alpha reduction of control incubations was similar in the 2 types of tumors. In the hormone-dependent tumors incubations containing estradiol showed 25-65% less 5alpha reduction than control incubations. In hormone-independent tumors estradiol did not inhibit 5alpha reduction. The effects of estradiol in decreasing tumor synthesis of 5alpha-reduced steroids are in keeping with the growth-promoting effects of estradiol in hormone-dependent tumors.
Portions of tumors from 41 patients with benign breast disease, 105 with breast cancer, and 6 of normal breast tissue were studied. Tissues were stored up to 1 month at -20 degrees C in air-tight containers prior to assay. Of the 41 benign tumors 3 had measurable receptor sites. 69 of the 105 cancers showed receptor sites, mostly of a higher order than the benign group. There was a statistically significant difference (p= .02) between the binding site concentration in the malignant tumors from pre- and postmenopausal patients. Concentrations were greater in the postmenopausal patients. The addition of increasing concentrations of dithioerythritol (DTT) in the buffers was found to enhance progressively the affinity for binding in 4 of tumors. In the 6 normal breast tissues, 2 sowed binding with DTT but none by the standard method. Using DTT to increase the sensitivity of the method may improve the prediction of later response to hormone manipulation.
Fabry's disease,1 heretofore a rare and esoteric diagnostic rubric, has become an important focus for research by biochemists, enzymologists, geneticists, clinical investigators and transplant surgeons.2 As noted by Clarke and his colleagues in this issue of the Journal, several centers have transplanted normal kidneys into patients with renal failure secondary to Fabry's disease. Of the nine patients throughout the world who have received transplants, four have had normal renal function for periods of six months to over three years.3 , 4 These successful transplants have had documented clinical improvement, with subjective relief of their frequent excruciating pain, return of sweating and . . .
