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Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.
- Source :
-
JNCI: Journal of the National Cancer Institute . 1/2/2002, Vol. 94 Issue 1, p50-60. 11p. 5 Color Photographs, 3 Charts. - Publication Year :
- 2002
-
Abstract
- <bold>Background: </bold>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-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis.<bold>Methods: </bold>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-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided.<bold>Results: </bold>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-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P</=.002) induced by progestin treatment.<bold>Conclusions: </bold>Progestin induces differential regulation in the ovarian epithelium of TGF-beta, 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TRANSFORMING growth factors-beta
*APOPTOSIS
*PROGESTATIONAL hormones
*ANIMAL experimentation
*COMPARATIVE studies
*EPITHELIUM
*GROWTH factors
*IMMUNOHISTOCHEMISTRY
*RESEARCH methodology
*MEDICAL cooperation
*ORAL contraceptives
*OVARIES
*PRIMATES
*RESEARCH
*EVALUATION research
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00278874
- Volume :
- 94
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- JNCI: Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 6538128
- Full Text :
- https://doi.org/10.1093/jnci/94.1.50