Scavenger receptor class B type I in the rat ovary: Possible role in high density lipoprotein cholesterol uptake and in the recognition of apoptotic granulosa cells

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol a s substrate for steroid hormone production. However, SR-BI also binds anion ic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the exp ression of SR-BI in rat ovarian follicles undergoing atresia. Atretic folli cles with cells undergoing apoptosis were identified by in situ DNA end lab eling, and SR-BI expression was determined by in, situ hybridization and im munohistochemistry. SR-BI was expressed in thecal cells at all stages of fo llicular development, including atretic follicles, and in corpus luteum. Is olated apoptotic granulosa cells (but not viable granulosa cells) bound ann exin V, indicating that they display anionic phospholipids on the cell surf ace. Transfection of COS-7 cells with an expression vector carrying the rat SR-BI complementary DNA resulted in increased binding to apoptotic granulo sa cells (46 +/- 2% of the SR-BI-expressing cells bound at least one granul osa cell compared with 24 +/- 3% for the mock-transfected cells; P < 0.0001 ), whereas the binding to viable granulosa cells was unchanged. Apoptotic g ranulosa cells also bound to isolated thecal shells. We conclude that theca l cells of both non-atretic and atretic follicles express SR-BI. The locati on of SR-BI expression in the ovary supports a role of this receptor in the uptake of high density lipoprotein cholesterol. In addition, our data sugg est that SR-BI mediates the recognition of apoptotic granulosa cells by the surrounding thecal cells and that it therefore may play a role in the remo deling of atretic follicles to secondary interstitial cells.