Presence of distinct cis-acting elements on gonadotropin gene promoters in diverse species dictates the selective recruitment of different transcription factors by steroidogenic factor-1

Abstract

The nuclear receptor steroidogenic factor-1 (SF-1) regulates the cell-specific expression of the pituitary gonadotropin subunit genes. Several potential DNA-binding sites for SF-1, estrogen receptor (ER) and the immediate-early transcription factor NGFI-A are found in LH β genes from many species. In this study, we have examined the action and interaction of these transcription factors on LH β gene promoters from two representative vertebrate species, i.e. rat and salmon. Cotransfection studies in COS-1 cells have shown that the action of SF-1 on salmon gonadotropin II β (sGTHII β) gene promoter was dramatically enhanced when combined with ER. The rat LH β promoter was activated by SF-1 or ER individually, but these two factors, however, were unable to act in synergism on this promoter. In contrast, NGFI-A, specifically in cooperation with SF-1, transactivated the rat LH β gene expression but was ineffective on the sGTHII β gene. Gel shift experiments showed that this lack of activation was due to the low affinity of the salmon NGFI-A-responsive element for its binding protein. In conclusion, our studies demonstrate that differential recruitment of distinct transcription factors by SF-1 might be a common mechanism to activate the cell-specific gonadotropin gene expression in different species.