Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.
Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.
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孕激素诱导的猕猴卵巢上皮细胞凋亡:转化生长因子-β的差异调节。
DOI:
10.1093/jnci/94.1.50
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发表时间:
2002
期刊:
影响因子:
--
通讯作者:
Hughes,ClaudeL
中科院分区:
文献类型:
--
作者:
Rodriguez,GustavoC;Nagarsheth,NimeshP;Lee,KarenL;Bentley,RexC;Walmer,DavidK;Cline,Mark;Whitaker,ReginaS;Isner,Pam;Berchuck,Andrew;Dodge,RichardK;Hughes,ClaudeL
Background:Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-β (TGF-β). We determined the effect of progestin on TGF-β expression in the primate ovarian epithelium and examined the relationship between TGF-β expression and apoptosis.Methods:Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-β1 or TGF-β2 plus TGF-β3 (TGF-β2/3) isoforms. The expression of TGF-β isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-β expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided.Results:Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-β1 and a concomitant increase in the expression of the TGF-β2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-β2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-β2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-β1 (P<.001) to TGF-β2/3 (P≤.002) induced by progestin treatment.Conclusions:Progestin induces differential regulation in the ovarian epithelium of TGF-β, a change in the expression of which is highly associated with apoptosis. These data suggest a possible biologic mechanism for the protective association between OC use and reduced ovarian cancer risk.
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影响因子:
3.5
作者:
GEISER, AG;BUSAM, KJ;SPORN, MB
通讯作者:
SPORN, MB
DOI:
10.1073/pnas.92.10.4254
发表时间:
1995-05-09
影响因子:
11.1
作者:
PIERCE, DF;GORSKA, AE;MOSES, HL
通讯作者:
MOSES, HL
DOI:
--
发表时间:
1997
期刊:
Oncology research.
影响因子:
--
作者:
Reiss,M
通讯作者:
Reiss,M
影响因子:
4.7
作者:
H. Thompson;A. Wilson;Junxuan Lu;Meenakshi Singh;Cheng Jiang;P. Upadhyaya;K. El-Bayoumy;C. Ip
通讯作者:
H. Thompson;A. Wilson;Junxuan Lu;Meenakshi Singh;Cheng Jiang;P. Upadhyaya;K. El-Bayoumy;C. Ip
DOI:
10.1016/0002-9378(92)91697-9
发表时间:
1992-02-01
影响因子:
9.8
作者:
BERCHUCK, A;RODRIGUEZ, G;BAST, RC
通讯作者:
BAST, RC