Lipoprotein enhancement of ovarian theca-interstitial cell steroidogenesis: relative contribution of scavenger receptor class B (type I) and adenosine 5'-triphosphate- binding cassette (type A1) transporter in high-density lipoprotein-cholesterol transport and androgen synthesis.
The theca-interstitial cells take up plasma high-density lipoprotein (HDL)- and low-density-lipoprotein-derived cholesterol to convert into steroid hormones. The uptake of HDL-derived cholesterol is mediated by the scavenger receptor, class B, type I (SR-BI). In nonsteroidogenic cells, HDL-stimulated efflux of cholesterol has been shown to be mediated by the ATP-binding cassette A1 (ABCA1) transporter. Its expression has not been documented in steroidogenic cells. The goal of the present study was to determine: 1) the role of SR-BI in theca-interstitial cell androgen production; 2) whether theca-interstitial cells express ABCA1 transporter mRNA; and 3) the relative roles of SR-BI and ABCA1 transporter in androgen production. The ABCA1 transporter mRNA expression in rat theca-interstitial cells was shown using RT-PCR and Northern blot analyses. The role of SR-BI and ABCA1 in androstenedione production was also examined by treating cells with anti-SR-BI and 2-hydroxypropyl-beta-cyclodextrin in the presence and absence of human chorionic gonadotropin and/or human HDL(3). The treatment of theca-interstitial cells with anti-SR-BI antibody blocked more than 90% of HDL plus human chorionic gonadotropin-stimulated androstenedione production, and selective HDL-CE uptake. On the other hand, the use of inhibitors of ABCA1 transporter function had no discernible effect on HDL-supported androgen production. These data demonstrate that, although theca-interstitial cells express both SR-BI and ABCA1 transporter mRNA, the SR-BI pathway supplies the majority of the cholesterol required for androgen production. Furthermore, the present study presents evidence for a crucial role for SR-BI in HDL-mediated androgen production.
Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Qian
Q
Wu
Susan
S
Sucheta
Salman
S
Azhar
K M J
KM
Menon
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000735:Androstenedione / Q000096:biosynthesis*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018955:CD36 Antigens / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000493:pharmacokinetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008075:Lipoproteins, HDL / Q000493:pharmacokinetics*; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013799:Theca Cells / Q000166:cytology / Q000378:metabolism*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000906:Antibodies; D018955:CD36 Antigens; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D000735:Androstenedione