UC San Diego

In the anterior pituitary, GnRH and activin are key regulators of reproduction. Furthermore, GnRH and activin synergize to induce FSH[beta] gene expression. We have identified a novel region of the FSH[beta] promoter located at -23 from the transcriptional start site that is important for GnRH responsiveness. In addition, activin has been shown to exert its effects on FSH[beta] gene transcription through Smad transcription factors as well as through the newly identified transcription factor FoxL2. In the mouse FSH[beta] promoter, we identified the FoxL2 sites at -350 and -120 to be most critical for activin induction, FoxL2 induction as well as for the synergistic induction by activin and GnRH. There seems to be controversy regarding the necessity of Smad binding sites adjacent to FoxL2 sites to convey activin responsiveness in different species. Therefore, we sought to determine whether FoxL2 or Smad binding site is a critical player in human FSH[beta] promoter by focusing on the homologous site at -132 from the transcriptional start site