Developmental and hormonal regulation of murine scavenger receptor, class B, type 1

The scavenger receptor, class B, type I (SR-BI), is the predominant recepto r that supplies plasma cholesterol to steroidogenic tissues in rodents. We showed previously that steroidogenic factor-1 (SF-1) binds a sequence in th e human SR-BI promoter whose integrity is required for high-level SR-BI exp ression in cultured adrenocortical tumor cells. We now provide in vivo evid ence that SF-1 regulates SR-BI. During mouse embryogenesis, SR-BI mRNA was initially expressed in the genital ridge of both sexes and persisted in the developing testes but not ovary. This sexually dimorphic expression profil e of SR-BI expression in the gonads mirrors that of SF-1. No SR-BI mRNA was detected in the gonadal ridge of day 11.5 SF-1 knockout embryos. Both SR-B I and SF-1 mRNA were expressed in the cortical cells of the nascent adrenal glands. These studies directly support SF-1 participating in the regulatio n of SR-BI in vivo. We examined the effect of cAMP on SR-BI mRNA and protei n in mouse adrenocortical (Y1-BS1) and testicular carcinoma Leydig (MA-10) cells. The time courses of induction were strikingly similar to those descr ibed for other cAMP- and SF-1-regulated genes. Addition of lipoproteins red uced SR-BI expression in Y1-BS1 cells, an effect that was reversed by admin istration of cAMP analogs. SR-BI mRNA and protein were expressed at high le vels in the adrenal glands of knockout mice lacking the steroidogenic acute regulatory protein; these mice have extensive lipid deposits in the adreno cortical cells and high circulating levels of ACTH. Taken together, these s tudies suggest that trophic hormones can override the suppressive effect of cholesterol on SR-BI expression, thus ensuring that steroidogenesis is mai ntained during stress.