Original Article

An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17-hydroxylase, C_17–20 lyase

Correspondence to: Cheryl A. Dyer.

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 17-hydroxylase, C_17–20 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 17-hydroxylase, C_17–20 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 17-hydroxylase, C_17–20 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 17-hydroxylase, C_17–20 lyase, in part through its interaction with apolipoprotein E-specific receptors of the LDL receptor superfamily.—Zhang, G., L. K. Curtiss, R. L. Wade, and C. A. Dyer. An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17-hydroxylase, C_17–20 lyase. J. Lipid Res. 1998. 39: 2406–2414.

Supplementary key words: androgen, RT-PCR, P450 cholesterol side-chain cleavage, receptor-associated protein, LDL receptor superfamily, steroidogenesis

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