Apolipoprotein E is a putative autocrine regulator of the rat ovarian theca cell compartment.
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.
Zerbinatti
C V
CV
Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86011-5640, USA.
Mayer
L P
LP
Audet
R G
RG
Dyer
C A
CA
D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005496:Follicular Atresia; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000502:physiology; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D001057:Apolipoproteins E; D007328:Insulin; D010446:Peptide Fragments; D011973:Receptors, LDL; D000735:Androstenedione; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases