SUMMARYWe investigated whether inter!eukin-6 (TL-6) could cause the release of corticoslerone by a direct interaction with the adrenal gland. Primary cultures of rat adrenal glands were obtained by dispersion with collagenase and incubated for 24 h with different doses or IL-6. Levels of corticosterone were measured by competitive protein binding assay. A significant (JP< 0-025) dosedependent increase in corticostei'one levels was seen al all doses ttsed. Time course experiments demonstrated that rL-6 stimulated corticosterone release over a period of 24 h but not after 12 or 3 h. The stimtilation of adrenal ceils with different doses of ACTHisj and 40 U/ml of rL-6 showed a synergistic effect when IL-6 was combined with low concentrations of ACTHi-24 (2 and 20 pmol//). Tills effect was not evident at higher doses. Our results suggest that lL-6 may act at different levels of the hypothalmic pituitary adrenal axis. Moreover the finding ofa synergistic effect with ACTH 1-24 indicates that IL~6 could play a rote In the long term response lo slcess.
Chronic treatment with the GnRH (gonadotrophin hormone releasing hormone) agonist Zoladex causes suppression of testicular androgens. Use of antiandrogens has been advocated to block the effects of the initial surge of androgens, and to block any presumed effects of adrenal androgens. We have measured plasma concentrations of androgens and possible precursors before and during treatment in the following prostate cancer patients: 10 who received Zoladex alone (Z), nine who received Zoladex + the anti-androgen flutamide (Z + F) and five who were orchidectomized (O). Testosterone fell in the Z + F group to 0.84 +/- 0.21 nmol/l (mean +/- SD) significantly lower (Wilcoxon P less than 0.05) than after Z (1.58 +/- 1.84 nmol/l) alone. Progesterone and 17 alpha-hydryxyprogesterone did not change significantly in any group. Androstenedione and dehydroepiandrosterone sulphate (DHAS) showed significant falls in Z + F (from 3.44 +/- 0.34 to 1.92 +/- 0.18 mumol/l and from 3.88 +/- 0.64 to 1.92 +/- 0.36 mumol/l respectively) but not in other groups. These results are consistent with our demonstration of an inhibitory effect of flutamide, hydroxyflutamide and other antiandrogens on human adrenal microsomal 17 alpha-hydroxylase and 17,20-lyase activities in vitro.
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