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Volume 271, Number 29, Issue of July 19, 1996 pp. 17425-17432
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Expression and Regulation of the Lipoprotein Lipase Gene in Human Adrenal Cortex

(Received for publication, December 1, 1996, and in revised form, April 22, 1996)

Bart Staels , Geneviève Martin , Monica Martinez ^§ , Caroline Albert ^¶ , Julia Peinado-Onsurbe , Régis Saladin , Dean W. Hum ^¶ , Manuel Reina ^§ , Senen Vilaro ^§ and Johan Auwerx

From U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, 1 Rue Calmette, 59019 Lille, France, the ^§ Department of Cell Biology, University of Barcelona, Avda. Diagonal 645, Barcelona (08028), Spain, the  Department of Biochemistry and Molecular Biology, University of Barcelona, Spain, and the ^¶ Laboratoire d'Endocrinologie Moléculaire, Le Centre Hospitalier de l'Université Laval, 2705 Blvd. Laurier, Québec, G1V 4G2 Canada

Lipoprotein lipase (LPL), an enzyme which hydrolyzes triglycerides and participates in the catabolism of remnant lipoproteins, plays a crucial role in energy and lipid metabolism. The goal of this study was to analyze the expression and regulation of the LPL gene in human adrenals. Reverse transcriptase-polymerase chain reaction amplification and sequence analysis demonstrated the presence of LPL mRNA in fetal and adult human adrenal cortex. Furthermore, the human adrenocortical carcinoma cell line, NCI-H295, expresses LPL mRNA and protein, which is localized to the outer cellular membrane as demonstrated by immunofluorescence confocal microscopy and can be released in the medium by heparin addition. To asses whether the LPL gene is regulated by agents regulating adrenal steroidogenesis, NCI-H295 cells were treated with activators of second messenger systems. Whereas the calcium-ionophore A23187 did not affect LPL gene expression, treatment with phorbol 12-myristate 13-acetate decreased LPL mRNA levels in a time- and dose-dependent manner. This decrease after phorbol 12-myristate 13-acetate was associated with diminished heparin-releasable LPL mass and activity in the culture medium. Addition of the cAMP analog 8-Br-cAMP to NCI-H295 cells resulted in a rapid, but transient dose-dependent induction of LPL mRNA. Treatment with the protein synthesis inhibitor cycloheximide gradually induced, whereas simultaneous addition of cAMP and cycloheximide superinduced LPL mRNA levels. Nuclear run-on analysis indicated that the effects of cAMP and cycloheximide occurred at the transcriptional and post-transcriptional level, respectively. Transient co-transfection assays demonstrated that the first 230 base pairs of the proximal LPL promoter contain a cAMP-responsive element activated by protein kinase A and transcription factors belonging to the CREB/CREM family. These data indicate that LPL is expressed in human adrenal cortex and regulated in NCI-H295 adrenocortical carcinoma cells by activators of the protein kinase A and protein kinase C second messenger pathways in a manner comparable to P450scc, which catalyzes the first step in adrenal steroidogenesis. These observations suggest a role for LPL in adrenal energy and/or lipid metabolism and possibly in steroidogenesis.

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