Structure-effect relationship in the induction of mitotic phase-specific abnormality of centrosome integrity and multipolar spindles by steroidal estrogens and their derivatives in cultured mammalian cells

T. Ochi, T. Oda

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In order to determine the structure-effect relationship in the induction of centrosome disintegrity (abnormality of γ-tubulin signals) and multipolar spindles in a cultured fibroblast cell line V79 by steroidal estrogens, the activities of various estrogens and their derivatives were investigated. Induction of centrosome disintegrity by estrogens was specific in cells in the mitotic phase and was not observed in interphase cells. The centrosome disintegrity induced 24 h after exposure to estrogens was accompanied by the appearance of multinucleated cells, but the microtubule network was organized. The rank order of potency of estrogens in inducing mitotic phase-specific centrosome disintegrity and multipolar spindles was as follows: 2-methoxyestradiol > dihydroequilin 3-methyl ether = equilin 3-methyl ether > 17α-estradiol > 17β-estradiol 3-methyl ether = 17β-estradiol > dihydroequilin > estrone 3-methyl ether. Equilin and estrone were not effective in causing centrosome disintegrity. These results suggest that the 17-hydroxyl group, irrespective of whether it is the sterically alpha or beta form, is necessary for estradiol and dihydroequilin to cause centrosome disintegrity and that O-methylation at the C-3 position was effective for equilin and dihydroequilin in enhancing the centrosome abnormality. 2-Methoxyestradiol was the most potent inducer of the centrosome disintegrity among the tested compounds and caused the induction of multiple signals of γ-tubulin, including more than five signals.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume78
Issue number2
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • 2-Methoxyestradiol
  • Centrosome
  • Estrogens
  • Microtubule
  • Multipolar spindle
  • γ-Tubulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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