Hepatic lipase gene expression is transiently induced by gonadotropic hormones in rat ovaries

Abstract

Hepatic lipase (HL) gene expression was studied in rat ovaries. A transcript lacking exons 1 and 2 could be detected by reverse transcription-polymerase chain reaction (RT-PCR) in the ovaries of mature cyclic females and of immature rats treated with pregnant mare serum followed by human chorionic gonadotropin (hCG) to induce superovulation. By competitive RT-PCR the HL transcript was quantified. Low levels of HL mRNA were detected in ovaries of mature cyclic females and of immature rats. During superovulation HL mRNA was several fold higher than in mature cyclic rats and transiently increased to a maximum at 2 days after hCG treatment. Pulse-labelling of ovarian cells and ovarian slices with [ 35 S]methionine followed by immunoprecipitation with polyclonal anti-HL IgGs showed de novo synthesis of a 47 kDa HL-related protein. Expression of the protein was transiently induced by gonadotropins with a peak at 2 days after hCG treatment. Induction of liver-type lipase activity occurred only after HL mRNA and synthesis of the HL-related protein had returned to pre-stimulatory levels. We conclude that in rat ovaries the HL gene is expressed into a variant mRNA and a 47 kDa protein. The expression of the HL gene in ovaries is inducible and precedes the expression of the mature, enzymatically active liver-type lipase.

Transient induction of a variant hepatic lipase messenger RNA by corticotropic hormone in rat adrenals

“…In rat adrenals and ovaries, the HL gene is not expressed into the full-length HL messenger RNA (mRNA). Instead, an alternative form of HL mRNA is found in these tissues [18,19], in which the first 2 coding exons of the HL gene are replaced by an intron-like sequence of unknown origin. We designate this novel sequence as exon 1A.…”

Hepatic lipase expression in macrophages contributes to atherosclerosis in apoE-deficient and LCAT-transgenic mice

“…HL is synthesized primarily by hepatocytes but is also present in steroidogenic tissues (1)(2)(3). The enzyme hydrolyzes triglycerides (TGs) and phospholipids (PLs) in chylomicron remnants (CRs), IDL, and HDL, thereby altering lipoprotein size and density (1,4,5).…”

Cloning, expression, and promoter analysis of hepatic lipase derived from human hyperplastic adrenals

“…The presence of full-length HL mRNA in the human adrenals contrasts with the situation in rat adrenals (19,22) and ovaries (20), where only a variant HL gene transcript is found. This variant HL mRNA is also present in rat liver, but at a low abundance relative to fulllength HL mRNA (19), and originates from the usage of an alternative promoter in intron-2 (22).…”

“…This is mainly based on the inability to detect full-length HL mRNA (7,9,(18)(19)(20) and de novo synthesis of HL protein (9,(18)(19)(20) in extrahepatic tissues of the rat. HL protein is present in rat plasma associated with HDL (4), and rat ovaries were shown to accumulate HL from the circulation (7).…”

“…However, expression of HL mRNA and synthesis of HL protein have now been demonstrated in adrenals of neonatal mice (10) and in human and mouse macrophages (21). We recently showed that the HL gene is transcribed in rat adrenals and ovaries, but exclusively from an alternative promoter within intron-2 (19,20,22). This gave a variant HL mRNA product in which the first two coding exons of the HL gene are substituted by a sequence that corresponds to intron-2 immediately upstream of exon-3.…”