The Basic Helix-Loop-Helix, Leucine Zipper Transcription Factor, USF (Upstream Stimulatory Factor), Is a Key Regulator of SF-1 (Steroidogenic Factor-1) Gene Expression in Pituitary Gonadotrope and Steroidogenic Cells

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Abstract
Tissue-specific expression of the mammalian FTZ-F1 gene is essential for adrenal and gonadal development and sexual differentiation. The FTZ-F1 gene encodes an orphan nuclear receptor, termed SF-1 (steroidogenic factor-1) or Ad4BP, which is a primary transcriptional regulator of sev- eral hormone and steroidogenic enzyme genes that are critical for normal physiological function of the hypothalamic-pituitary-gonadal axis in repro- duction. The objective of the current study is to understand the molecular mechanisms underlying transcriptional regulation of SF-1 gene expression in the pituitary. We have studied a series of deletion and point mutations in the SF-1 promoter region for transcriptional activity in aT3-1 and LbT2 (pitu- itary gonadotrope), CV-1, JEG-3, and Y1 (adreno- cortical) cell lines. Our results indicate that maxi- mal expression of the SF-1 promoter in all cell types requires an E box element at 282/277. This E box sequence (CACGTG) is identical to the bind- ing element for USF (upstream stimulatory factor), a member of the helix-loop-helix family of tran- scription factors. Studies of the SF-1 gene E box element using gel mobility shift and antibody su- pershift assays indicate that USF may be a key transcriptional regulator of SF-1 gene expression. (Molecular Endocrinology 12: 714-726, 1998)

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