The regulation of aromatase activity in breast fibroblasts: the role of interleukin-6 and prostaglandin E-2

Prostaglandin E-2 (PGE(2)) and cytokines, such as interleukin-6 (IL-6) or t umour necrosis factor alpha (TNF alpha) can regulate aromatase activity. In the present study we have compared their abilities to stimulate aromatase activity in fibroblasts derived from 'normal' breast adipose tissue proxima l to a tumour or breast tumours. PGE(2), TNF alpha and IL-6 plus its solubl e receptor (IL-6sR) all increased aromatase activity in these cells. Basal aromatase activity and the degree of aromatase stimulation by these factors were greater in fibroblasts derived from 'normal' breast tissue than from breast tumours. The ability of IL-6+IL-6sR to increase aromatase activity w as only marginally reduced by the PG synthesis inhibitor, indomethacin, ind icating that IL-6+IL-6sR does not appear to act via induction of PG synthes is. The ability of PGE(2) to stimulate aromatase activity in fibroblasts de rived from 'normal' breast tissue was potentiated by IL-6sR suggesting that PGE(2) may act via induction of IL-6. This was confirmed by measurement of IL-6 in conditioned medium collected from these cells. A significant incre ase in IL-6 concentrations was detected in conditioned medium collected fro m cells treated with PGE(2). It is concluded that in some fibroblasts PGE(2 ) may exert part of its regulatory effect on breast tissue aromatase activi ty via induction of IL-6.