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Biology of Reproduction 61, 665-672 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.


Articles

Apolipoprotein E Peptide Stimulation of Rat Ovarian Theca Cell Androgen Synthesis Is Mediated by Members of the Low Density Lipoprotein Receptor Superfamily1

Celina V. Zerbinatti2,a, and Cheryl A. Dyera

a Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86011

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 theca 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)2C or acetyl-Y(141–155)2C, has low density lipoprotein (LDL) receptor and LDL receptor-related protein-binding activity, and it mimics the activity of native apo E in the theca-interstitial cell system. To define the role of members of the LDL receptor superfamily in the apo E peptide-mediated responses, we found that receptor-associated protein prevented the stimulation without altering the inhibition of androstenedione production. The apo E peptide (129–162), which has no LDL receptor-binding activity, did not stimulate androstenedione production. The apo E peptide acetyl-Y(141–155)2C did not stimulate androstenedione production when cell surface heparan sulfate proteoglycans were degraded with heparinase. The apo E peptide acetyl-Y(141–155)2C bound to heparin, a property of LDL receptor ligands, and in this complex the peptide had no effect on androstenedione production. These observations support the conclusion that apo E-mediated stimulation, but not inhibition, of ovarian theca cell androstenedione production was mediated by members of the LDL receptor superfamily.

1 Supported by NIH Grant HD27167 and an American Heart Association Established Investigatorship Award to C.A.D.

2 Correspondence: Celina V. Zerbinatti, Department of Biological Sciences, South Beaver St., Room 420, Box 5640, Northern Arizona University, Flagstaff, AZ 86011–5640. FAX: 520 523 7500; celina.zerbinatti{at}nau.edu




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