THE BASIC HELIX-LOOP-HELIX, LEUCINE-ZIPPER TRANSCRIPTION FACTOR, USF (UPSTREAM STIMULATORY FACTOR), IS A KEY REGULATOR OF SF-1 (STEROIDOGENIC FACTOR-I) GENE-EXPRESSION IN PITUITARY GONADOTROPE AND STEROIDOGENIC CELLS

Tissue-specific expression of the mammalian FTZ-F1 gene is essential f or adrenal and gonadal development and sexual differentiation. The FTZ -F1 gene encodes an orphan nuclear receptor, termed SF-1 (steroidogeni c factor-1) or Ad4BP, which is a primary transcriptional regulator of several hormone and steroidogenic enzyme genes that are critical for n ormal physiological function of the hypothalamic-pituitary-gonadal axi s in reproduction. 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 deleti on and point mutations in the SF-1 promoter region for transcriptional activity in alpha T3-1 and L beta T2 (pituitary gonadotrope), CV-1, J EG-3, and Y1 (adrenocortical) cell lines. Our results indicate that ma ximal expression of the SF-1 promoter in all cell types requires an E box element at -82/-77. This E box sequence (CACGTG) is identical to t he binding element for USF (upstream stimulatory factor), a member of the helix-loop-helix family of transcription factors. Studies of the S F-1 gene E box element using gel mobility shift and antibody supershif t assays indicate that USF may be a key transcriptional regulator of S F-1 gene expression.