Divergent mechanisms regulate proliferation/survival and steroidogenesis of theca-interstitial cells

被引:20
作者
Duleba, AJ
Spaczynski, RZ
Olive, DL
Behrman, HR
机构
[1] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA
[2] Karol Marcinkowski Univ, Sch Med Sci, Dept Obstet & Gynecol, Poznan, Poland
关键词
IGF-I; LH; proliferation; steroidogenesis; theca-interstitial cells;
D O I
10.1093/molehr/5.3.193
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Luteinizing hormone (LH) and insulin-like growth factor I (IGF-I) are recognized as major regulators of ovarian theca-interstitial (T-l) function. This study was designed to compare the effects of LH and IGF-I on T-l proliferation and steroidogenesis. Purified rat T-l cells were cultured in chemically-defined media. DNA synthesis was evaluated by a radiolabelled thymidine incorporation assay. The cells were also directly counted. Progesterone production was assessed using a specific radioimmunoassay, DNA synthesis of T-l cells was stimulated by IGF-I (10 nM) but modestly inhibited by LH (100 ng/ml). The inhibitory effect of LH was mimicked by 8Br-cAMP (10(-4) to 10(-3) M); forskolin (10(-5) M), cholera toxin (10 ng/ml) and 3-isobutyl-methyl-xanthine (10(-5) M). Stimulation of protein kinase C with phorbol 12-myristate 13-acetate (10(-7) M) had no significant effect on DNA synthesis, Furthermore, DNA synthesis was not affected by testosterone (10(-10) to 10(-9)M) or progesterone (10(-9) to 10(-8) M). Accumulation of progesterone was co-operatively stimulated by LH and IGF-I, These results suggest that LH-induced inhibition of T-l proliferation and/or survival is mediated via the cAMP system. IGF-I may be viewed as a co-gonadotrophin with respect to steroidogenesis but not with respect to proliferation/survival. The divergence of the effects on proliferation/survival versus steroidogenesis underscores the complexity of the interactions between LH and IGF-I signalling pathways.
引用
收藏
页码:193 / 198
页数:6
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