Apolipoprotein E is a putative autocrine regulator of the rat ovarian theca cell compartment

C. V. Zerbinatti, L. P. Mayer, R. G. Audet, C. A. Dyer

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Apolipoprotein (apo) E inhibits androgen production by ovarian theca cells. We found that apo E, as a synthetic peptide mimicked the full-size protein, induced theca and interstitial cell (TIC) apoptosis indicated by pyknotic cell morphology, increased DNA end-labeling (TUNEL), and DNA ladders. None of the low-density lipoprotein (LDL) receptor superfamily members were involved because the universal antagonist of these receptors, receptor-associated protein (RAP), did not block apo E-induced apoptosis. Furthermore, several apo E synthetic peptides that do not bind the LDL receptor did induce TIC apoptosis. Similar to apo E, apoptogenic agents such as ceramide and LY 294002, a phosphatidylinositol (PI) 3-kinase inhibitor, induced apoptosis and suppressed androstenedione production. However, apoptosis alone was not responsible for apo E suppression of androstenedione production because both insulin and IGF-I prevented apo E-induced apoptosis, but neither restored androstenedione production. Theca cells of atretic follicles express the greatest apo E mRNA, and here we show that cultured TIC produce apo E. When considered with the observation of TUNEL-positive theca cells in atretic follicles these results support our hypothesis that intraovarian apo E controls theca cell production of androgen as well as limiting the size of the theca cell compartment.

Original languageEnglish (US)
Pages (from-to)1080-1089
Number of pages10
JournalBiology of reproduction
Volume64
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Apoptosis
  • Insulin
  • Theca cells

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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