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Pituitary Homeobox 1 Activates the Rat FSHß (rFSHß) Gene through Both Direct and Indirect Interactions with the rFSHß Gene Promoter

Endocrine-Hypertension Division (M.M.Z., K.-H.J., C.L., U.B.K.), Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Endocrine Division (M.M.Z.), Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Ursula B. Kaiser, Endocrine-Hypertension Division, Brigham & Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: ukaiser{at}partners.org.

Molecular mechanisms underlying gonadotrope-specific and hormonal regulation of FSHß gene expression remain largely unknown. We have studied the role of pituitary homeobox 1 (Ptx1), a transcription factor important for regulation of many pituitary-specific genes, in the regulation of rat FSHß (rFSHß) gene transcription. We demonstrate that Ptx1 activates the rFSHß gene promoter both basally and in synergy with GnRH. The effect of Ptx1 was localized to -140/-50, a region also important for basal activity of the promoter. Two putative Ptx1 binding sites (P1 and P2) homologous to consensus Ptx1 binding elements were identified in this region. We demonstrate specific binding of Ptx1 to the P2 but not to the P1 site. Furthermore, functional studies indicate that the P2 but not the P1 site mediates activation of the promoter by Ptx1. Residual activation of the promoter by Ptx1 was observed independent of the P2 site. However, no additional Ptx1 binding sites were identified in this region, indicating that the residual activation observed is likely independent of direct Ptx1 binding to the promoter. These results identify a functional Ptx1 binding site in the rFSHß gene promoter and suggest the presence of an additional activating pathway that is independent of direct binding of Ptx1 to the promoter.

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