The Intracellular Control of Aromatase Activity by 5α- Reduced Androgens in Human Breast Carcinoma Cells in Culture*

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Abstract
Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in α-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (-6, 10-7, and 10-8 M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10-8 M, with 5α-A-dione producing the greatest inhibition (50%). At 10-7 M, inhibition ranged from 45% (AND) to 70% (5α-A-dione), and at 10-6 M, inhibition was greater than 90% for each compound. 5α-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5α-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity.