Non-genomic effects of progestins -: inhibition of cell growth and increased intracellular levels of cyclic nucleotides

被引:24
作者
Sager, G [1 ]
Orbo, A
Jæger, R
Engström, C
机构
[1] Univ Tromso, Med Biol Inst, Fac Med, Dept Pharmacol, N-9037 Tromso, Norway
[2] Univ Tromso, Inst Med Biol, Fac Med, Dept Pathol, N-9037 Tromso, Norway
关键词
progestins; non-genomic effects; cell growth; cyclic nucleotides;
D O I
10.1016/S0960-0760(02)00269-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The anti-proliferative effect of progestins was studied in human transformed cell lines from the uterine cervix (C-4I, C33A and Me-180). Progestins caused a concentration-dependent inhibition of proliferation. The maximum tested concentration (2.6-3.2 muM) inhibited C-41 cell growth by the following orderof potency: progesterone (56%) > medroxyprogesterone (38%) > megestrol acetate (25%). The sensitivity, expressed as 125 (the concentration that caused 25% inhibition of growth), showed the same order: progesterone (7.7 nM) > medroxyprogesterone (78 nM) > megestrol acetate (570 nM). The intracellular levels of cGMP and cAMP were elevated and the cellular export of these cyclic nucleotides was inhibited by a similar order of potency. The C-41 cell line was devoid of progesterone-, estrogen-, androgen- and glucocorticoid-receptors. In addition, the antiprogestins mifepristone, onapristone and ZK-112993 did not block the anti-proliferative effect of progesterone. On the other hand, antiprogestins (2.3 nM) appeared to have some progesterone-like ("mimetic") activity with inhibition of C-41 cell growth; mifepristone (I I %), onapristone (12%) and ZK-112993 (16%). The observed effects of progestins and antiprogestins on C-41 cells were also presented in C33A cells (16% androgen receptor positive) and Me-180 cells (22% progesterone receptor positive, 9% androgen receptor positive and 17% glucocorticoid receptor positive). This study suggests that a non-genomic mechanism contributes to the anti-proliferative effect of progestins. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
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页码:1 / 8
页数:8
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