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Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.

Publication ,  Journal Article
Rodriguez, GC; Nagarsheth, NP; Lee, KL; Bentley, RC; Walmer, DK; Cline, M; Whitaker, RS; Isner, P; Berchuck, A; Dodge, RK; Hughes, CL
Published in: J Natl Cancer Inst
January 2, 2002

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-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. 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-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. 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-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

Duke Scholars

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

January 2, 2002

Volume

94

Issue

1

Start / End Page

50 / 60

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Progestins
  • Ovary
  • Oncology & Carcinogenesis
  • Macaca fascicularis
  • Immunohistochemistry
  • Female
  • Epithelium
  • Contraceptives, Oral, Hormonal
  • Apoptosis
 

Citation

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Rodriguez, G. C., Nagarsheth, N. P., Lee, K. L., Bentley, R. C., Walmer, D. K., Cline, M., … Hughes, C. L. (2002). Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta. J Natl Cancer Inst, 94(1), 50–60. https://doi.org/10.1093/jnci/94.1.50
Rodriguez, Gustavo C., Nimesh P. Nagarsheth, Karen L. Lee, Rex C. Bentley, David K. Walmer, Mark Cline, Regina S. Whitaker, et al. “Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.J Natl Cancer Inst 94, no. 1 (January 2, 2002): 50–60. https://doi.org/10.1093/jnci/94.1.50.
Rodriguez GC, Nagarsheth NP, Lee KL, Bentley RC, Walmer DK, Cline M, et al. Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta. J Natl Cancer Inst. 2002 Jan 2;94(1):50–60.
Rodriguez, Gustavo C., et al. “Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.J Natl Cancer Inst, vol. 94, no. 1, Jan. 2002, pp. 50–60. Pubmed, doi:10.1093/jnci/94.1.50.
Rodriguez GC, Nagarsheth NP, Lee KL, Bentley RC, Walmer DK, Cline M, Whitaker RS, Isner P, Berchuck A, Dodge RK, Hughes CL. Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta. J Natl Cancer Inst. 2002 Jan 2;94(1):50–60.

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

January 2, 2002

Volume

94

Issue

1

Start / End Page

50 / 60

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Progestins
  • Ovary
  • Oncology & Carcinogenesis
  • Macaca fascicularis
  • Immunohistochemistry
  • Female
  • Epithelium
  • Contraceptives, Oral, Hormonal
  • Apoptosis