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2002:
Val P; Aigueperse C; Lefrançois-Martinez A M; Jean Cl; Veyssière G; Martinez A
Role of three SF-1 binding sites in the expression of the mvdp/akr1-b7 isocaproaldehyde reductase in Y1 cells.
Endocrine research 2002;
28(
4):.
Mvdp/akr1-b7 encodes an aldose-reductase-like enzyme expressed in the zona fasciculata of the adrenal cortex, the function of which is essential for the detoxification of the cholesterol side chain cleavage product, isocaproaldehyde. The -510/+41 akr1-b7 promoter fragment is able to reproduce the endogenous gene zona fasciculata restricted, ACTH-controlled expression, in transgenic mice adrenals. Here, we report that three response elements contained within this promoter (positions -102, -458, -503) are able to bind SF-1, the essential regulator of steroidogenesis, although the low affinity site at -503 retains some other specific proteins present in Y1 nuclear extracts. Mutation of the -102 site results in a lowering of the activity of the -510/+41 promoter in Y1 cells, whereas mutation of the -458 site induces a reduction both in the global activity and forskolin sensitivity of the promoter. Interestingly, differential mutations of the -503 site nucleotides either induce an increase or a decrease in the basal and forskolin-induced activity.
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