Much effort has been devoted toward elucidating mechanisms underlying production of the gonadotropins. We have recently shown that the promoter from the bovine LHBeta (bLHB) gene confers gonadotrope- specific, as well as T E2, and GnRH responsive expression in transgenic mice. We have also shown that the promoter is regulated by a high-affinity binding site for SF-1, over expression of the transcription factor, Ptx1, activates a bLHB promoter construct in vitro. We hypothesize that multiple regulatory elements are involved in mediating expression of the bLHBeta gene. Therefore, two aims of this research are to; 1) Assess whether bLHBeta promoter represents a target for transcription factors Ptx1, P-Lim, and C-lim and assess possible synergistic interactions of Ptx1 with P-Lim, C-Lim or SF-1 to confer this expression~ and 2) Determine the functional importance of established protein binding sites within the bLHBeta promoter. Precise definition of regulatory elements that confer expression of the genes encoding LH subunits may also lead toward addressing the tenetic factors that contribute to the complex biology of the gonadotrope. While I will identify essential transcription factors, we have a vague understanding of the complete array of genes involved in maintaining a mature gonadotrope to this end, my third aim focuses on characterization of mRNAs that are differentially expressed between cell line representing gonadotrope precursor cells of similar lineage but whose phenotype differs in one critical aspect; that is, only one of these cell lines is capable of synthesizing and secreting LH. Completion of this project will significantly enhance our understanding of the molecular events involved in gonadotrope regulation.
| Quirk, Christine C; Seachrist, Darcie D; Nilson, John H (2003) Embryonic expression of the luteinizing hormone beta gene appears to be coupled to the transient appearance of p8, a high mobility group-related transcription factor. J Biol Chem 278:1680-5 |
| Quirk, C C; Lozada, K L; Keri, R A et al. (2001) A single Pitx1 binding site is essential for activity of the LHbeta promoter in transgenic mice. Mol Endocrinol 15:734-46 |
| Keri, R A; Bachmann, D J; Behrooz, A et al. (2000) An NF-Y binding site is important for basal, but not gonadotropin-releasing hormone-stimulated, expression of the luteinizing hormone beta subunit gene. J Biol Chem 275:13082-8 |
