Apoprotein E-rich high density lipoproteins inhibit ovarian androgen synthesis.
The influence of high density lipoproteins (HDL) on luteinizing hormone-stimulated rat ovarian theca/interstitial cell steroidogenesis was studied. Without HDL the cells produced primarily androgens from progestin precursors. In the presence of rat or human HDL steroid output increased 3-5-fold, but the type of steroid produced was dependent on the source of the HDL. Human HDL nonselectively amplified luteinizing hormone-stimulated steroid production, whereas rat HDL promoted progestin production without a concomitant increase in androgen output. Comparisons of the activities of apoprotein E-rich HDL (e.g. HDL from intact mature rats) with apoprotein E-poor HDL (e.g. human HDL or rat HDL from hypophysectomized immature rats) suggested that apoprotein E was responsible for the inhibition of androgen production. Furthermore, the inhibitory activity of rat HDL was abolished by depleting apoprotein E-containing lipoproteins with heparin affinity chromatography. Direct evidence that apoprotein E was the inhibitory constituent of rat HDL was obtained by showing that isolated lipid-free rat apoprotein E inhibited androgen production, whereas isolated rat apoproteins A-I and A-IV did not. The possible paracrine function of apoprotein E in ovarian follicular maturation of the ovary is discussed.
Dyer
C A
CA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Curtiss
L K
LK
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007016:Hypophysectomy; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000728:Androgens; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL