A STEROIDOGENIC FACTOR-I BINDING-SITE IS REQUIRED FOR ACTIVITY OF THELUTEINIZING-HORMONE BETA-SUBUNIT PROMOTER IN GONADOTROPES OF TRANSGENIC MICE

Analysis of luteinizing hormone (LH) beta subunit promoters from a bro ad range of species including teleosts and humans revealed strict cons ervation of a sequence homologous to the steroidogenic factor-1 (SF-1) regulatory element of cytochrome P-450 steroid hydroxylase genes. Int eraction between SF-1 and this putative response element in the bovine LH beta promoter was confirmed by electrophoretic mobility shift assa ys. Furthermore, cotransfection of alpha T3-1 cells with an expression vector encoding; SF-1 induced binding site-dependent transcription fr om the bovine LH beta promoter. Physiological significance of the LH b eta SF-1 consensus sequence was established using transgenic mice cont aining either the wild type bovine promoter or a promoter with a site- specific mutation of this site. Mutation of the SF-1 binding site near ly eliminated promoter activity, and the mutant transgene remained ina ctive following induction of gonadotropin-releasing hormone accomplish ed by castrating male and female mice. Thus, increases of gonadotropin -releasing hormone within a physiological range did not compensate for the loss of the SF-1 binding site. Together, these findings indicate that the SF-1 binding site is a key regulator of LH beta promoter acti vity in vivo and implicate SF-1 as at least one of the transcription f actors that acts through this site.