Estrogens play important roles in the development of breast cancer. Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist at high concentrations in breast cancer tissue. Although these cytokines are thought to exert some effect on cancer growth, their precise mechanism is still unclear. In the present study, we investigated the effects of inflammatory cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen-producing enzymes, and cell proliferation using human breast cancer cell lines (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS. Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7. Although IL-6 did not show significant effect on cell proliferation, cell proliferation was significantly increased when IL-6 and E1-S were simultaneously added to the incubation medium. This cell proliferative effect was apparently stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did not show any effect. These results led us to the hypothesis that inflammatory cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer cells through estrogen production by steroid-catalyzing enzymes in the tissue.
Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) were measured in patients with hyperadrenocorticism. When compared to normal subjects of corresponding age, serum DHEA-S levels were normal or elevated in 37 patients with Cushing's disease. In contrast, DHEA-S levels were significantly lower than those of normal subjects in all 28 patients with hyperadrenocorticism due to benign adrenocortical adenoma, suggesting that ACTH is the major determinant of DHEA-S secretion and that determination of serum DHEA-S concentrations is useful in the biochemical differential diagnosis of the etiology of Cushing's syndrome. In six patients with adrenocortical adenoma, the recovery of suppressed DHEA-S secretion after removal of the adrenal gland affected by a tumor was studied. Serum cortisol levels normalized by the end of the second year after unilateral adrenalectomy, while DHEA-S levels remained low for at least 2 succeeding yr. The results suggest that deficient ACTH secretion may result in a greater and longer lasting loss in the ability of the adrenal cortex to secrete androgens than in the ability to secrete cortisol.
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