An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17 alpha-hydroxylase, C17-20 lyase

Ovarian theca/interstitial cells produce androgens in response to luteinizi ng hormone (LH) stimulation and apolipoprotein (apo) E exerts a selective e ffect on the type of steroid product made by these cells, We have identifie d an apoE synthetic peptide containing the low density lipoprotein (LDL) re ceptor binding domain, acetyl-Y(LRK LRKRLLRDADDL)(2)C, that mimics the acti vity of native apoE, Depending on the concentration, the apoE synthetic pep tide either enhanced or inhibited the LH-stimulated production of androsten edione with concomitant changes in the mRNA for its synthetic enzyme, P450 17 alpha-hydroxylase, C17-20 lyase, without any changes in progesterone pro duction or the mRNA for its synthetic enzyme, P450 cholesterol side-chain c leavage, The apoE synthetic peptide caused changes in the rate of transcrip tion of the mRNA for P450 17a-hydroxylase, C17-20 lyase without altering it s stability, Pretreatment of the theca/interstitial cells with receptor-ass ociated protein, which blocks apoE binding to members of the LDL receptor s uperfamily, prevented the apoE synthetic peptide-mediated stimulation of an drostenedione and mRNA for P450 17 alpha-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/interstiti al cells by regulating the transcription of mRNA for the gene for P450 17a- hydroxylase, C17-20 lyase, in part through its interaction with apolipoprot ein E-specific receptors of the LDL receptor superfamily.