Apolipoprotein E peptide stimulation of rat ovarian theca cell androgen synthesis is mediated by members of the low density lipoprotein receptor superfamily

Ovarian androgen production is rate limiting for follicular maturation and can induce follicular atresia, Thus, it is important to define the actions of the intraovarian agents, such as apolipoprotein (apo) E, that modulate t heca cell androgen production. Theca cell androgen production is stimulated at low concentrations and inhibited at higher concentrations of native apo E. The apo E peptide, acetyl-Y(LRKLRKRLLRDADDL)(2)C or acetyl-Y(141-155)(2 )C, has low density lipoprotein (LDL) receptor and LDL receptor-related pro tein-binding activity, and it mimics the activity of native apo E in the th eca-interstitial cell system. To define the role of members of the LDL rece ptor superfamily in the apo E peptide-mediated responses, we found that rec eptor-associated protein prevented the stimulation without altering the inh ibition of androstenedione production. The apo E peptide (129-162), which h as no LDL receptor-binding activity, did not stimulate androstenedione prod uction, The apo E peptide acetyl-Y(141-155)(2)C did not stimulate androsten edione production when cell surface heparan sulfate proteoglycans were degr aded with heparinase. The apo E peptide acetyl-Y(141-155)(2)C bound to hepa rin, a property of LDL receptor ligands, and in this complex the peptide ha d no effect on androstenedione production, These observations support the c onclusion that apo E-mediated stimulation, but not inhibition, of ovarian t heca cell androstenedione production was mediated by members of the LDL rec eptor superfamily.