An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17alpha-hydroxylase, C17-20 lyase.
Ovarian theca/interstitial cells produce androgens in response to luteinizing hormone (LH) stimulation and apolipoprotein (apo) E exerts a selective effect on the type of steroid product made by these cells. We have identified an apoE synthetic peptide containing the low density lipoprotein (LDL) receptor binding domain, acetyl-Y(LRK LRKRLLRDADDL)2C, that mimics the activity of native apoE. Depending on the concentration, the apoE synthetic peptide either enhanced or inhibited the LH-stimulated production of androstenedione with concomitant changes in the mRNA for its synthetic enzyme, P450 17alpha-hydroxylase, C17-20 lyase, without any changes in progesterone production or the mRNA for its synthetic enzyme, P450 cholesterol side-chain cleavage. The apoE synthetic peptide caused changes in the rate of transcription of the mRNA for P450 17alpha-hydroxylase, C17-20 lyase without altering its stability. Pretreatment of the theca/interstitial cells with receptor-associated protein, which blocks apoE binding to members of the LDL receptor superfamily, prevented the apoE synthetic peptide-mediated stimulation of androstenedione and mRNA for P450 17alpha-hydroxylase, C17-20 lyase, but did not attenuate the inhibitory activity of the peptide. Thus, apolipoprotein E selectively altered the type of steroid made by ovarian theca/interstitial cells by regulating the transcription of mRNA for the gene for P450 17alpha-hydroxylase, C17-20 lyase, in part through its interaction with apolipoprotein E-specific receptors of the LDL receptor superfamily.
Zhang
G
G
Department of Biological Sciences, Northern Arizona University, Box 5640, Flagstaff, AZ 86011-5640, USA.
Curtiss
L K
LK
Wade
R L
RL
Dyer
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013799:Theca Cells / Q000201:enzymology*; D014158:Transcription, Genetic
D001057:Apolipoproteins E; D013254:Steroid 17-alpha-Hydroxylase