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M008556200v1
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Papers In Press, published online ahead of print January 16, 2001
J. Biol. Chem, 10.1074/jbc.M008556200
Submitted on September 19, 2000
Revised on January 16, 2001
Accepted on January 15, 2001

Progesterone stimulates ADD1/SREBP1c expression. Potential mechanism for the lipogenic effect of progesterone in adipose tissue

Daniele Lacasa, Xavier Le Liepvre, Pascal Ferré, and Isabelle Dugail

INSERM 465, Paris 75006

Corresponding Author: idugail{at}bhdc.jussieu.fr

Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme is transcriptionnally controlled by ADD1/SREBP1c, through insulin-mediated stimulation of ADD1/SREBP1c expression. Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumours cell lines upon progesterone treatment. We show here that progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue. In MCF7, progesterone induced ADD1/SREBP1c and Metallothionein II (a well-known progesterone-regulated gene) mRNAs, with comparable potency. In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional level. The membrane-bound and mature nuclear forms of ADD1/SREBP1 protein accumulated in preadipocytes cultured with progesterone, and FAS induction could be abolished by adenovirus-mediated overexpression of a dominant-negative form of ADD1/SREBP1 in these cells. Finally, in the presence of insulin, progesterone was unable to up-regulate ADD1/SREBP1c mRNA in preadipocytes, whereas its effect was restored after 24-hours of insulin deprivation. Together these results demonstrate that ADD1/SREBP1c is controlled by progesterone which, like insulin, acts by increasing ADD1/SREBP1c gene transcription. This provides a potential mechanism for the lipogenic actions of progesterone on adipose tissue.


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