Aspects of hepatic lipase expression : relation to cholesterol homeostasis

Hepatic lipase has triacylglycerol hydrolase and phospholipase A1 activity towards a wide variety of substrates. It is extracellularly localized in liver and in steroid hormone producing organs. The enzyme plays an important role in both intracellular cholesterol homeostasis and lipoprotein metabolism. Furthermore, in adrenal glands and ovaries the lipase activity may play a role in the cholesterol uptake from circulating lipoproteins to be used in hormone synthesis. In this process SR-BI may also be involved. In this study we intended to characterize the expression of the hepatic lipase in steroidogenic tissues under different conditions. Further, we studied its relation to the recently proposed putative HDL receptor, SR-BI, in the cholesterol homeostasis in those organs. In rat adrenals the full-length HL mRNA is absent but a variant form missing the first two exons could be detected. In rat adrenals and ovaries hepatic lipase activity is increased after stimulation with tropic hormones. We first intended to study the HL gene expression in rat ovaries after hormonal induction of superovulation and to investigate how gonadotropic hormones regulate the variant HL mRNA (Chapter 2.1.). Our results showed that trophic hormones modulate the variant HL mRNA and protein levels. Based on these observations we hypothesized that the variant HL mRNA would own an alternative promoter region involved in the enzyme expression in steroidogenic tissues. We proposed to localize this novel 5'-region, to identify a possible transcription start site and to study the regulation of this promoter (Chapter 2.2.). From our results it is not clear whether the HL activity found in rat ovaries and adrenal glands is a product of the variant HL mRNA or synthesized by the liver and transported to those organs. In an attempt to better understand this matter we studied the functional molecular mass of hepatic lipase i