Document Detail

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.
MedLine Citation:
PMID:  12746305     Owner:  NLM     Status:  MEDLINE    
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.
Qian Wu; Susan Sucheta; Salman Azhar; K M J Menon
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endocrinology     Volume:  144     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-14     Completed Date:  2003-06-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2437-45     Citation Subset:  AIM; IM    
Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
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MeSH Terms
ATP-Binding Cassette Transporters / genetics,  metabolism*
Androstenedione / biosynthesis*
Antibodies / pharmacology
Antigens, CD36 / immunology,  metabolism*
Cells, Cultured
Cholesterol Esters / pharmacokinetics
Gene Expression Regulation / physiology
Lipoproteins, HDL / pharmacokinetics*
Membrane Proteins*
RNA, Messenger / analysis
Rats, Sprague-Dawley
Receptors, Immunologic*
Receptors, Lipoprotein*
Receptors, Scavenger
Scavenger Receptors, Class B
Theca Cells / cytology,  metabolism*
Grant Support
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Antibodies; 0/Antigens, CD36; 0/Cholesterol Esters; 0/Lipoproteins, HDL; 0/Membrane Proteins; 0/RNA, Messenger; 0/Receptors, Immunologic; 0/Receptors, Lipoprotein; 0/Receptors, Scavenger; 0/Scarb1 protein, mouse; 0/Scarb1 protein, rat; 0/Scavenger Receptors, Class B; 63-05-8/Androstenedione

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