title: Pre-translational and post-translational regulation of TSH synthesis in normal and neoplastic thyrotrophs.
abstract: We are interested in the mechanisms by which endocrine and developmental factors regulate TSH synthesis at both pre-translational and post-translational levels. Thyroid hormone profoundly decreases transcription of the TSH-beta gene, while TRH and agents modifying cyclic AMP increase transcription. To elucidate the molecular mechanisms underlying these effects, human embryonal kidney cells were transfected with constructs of the human TSH-beta gene fused to the chloramphenicol acetyltransferase gene. The first exon of human TSH-beta, contains an element that increases basal expression and mediates T3-induced gene repression, probably through a direct interaction with c-erbA beta. This transcriptional repression by T3 appears aberrant in thyrotropic tumors. In contrast, TRH and agents modifying cyclic AMP mediate increased transcription of TSH-beta through interacting with upstream regulatory elements. Thyroid hormone, TRH and developmental factors also regulate the branching pattern and relative sialylation of TSH carbohydrate chains, which may affect TSH action in vitro and in vivo. Certain thyrotropic tumors produce TSH with more complex carbohydrate branching patterns, which may increase its biologic activity.
authors.affiliation: NIDDK, National Institutes of Health, Bethesda, Md.
authors.forename: B D
authors.initials: BD
authors.lastname: Weintraub
authors.forename: F E
authors.initials: FE
authors.lastname: Wondisford
authors.forename: E A
authors.initials: EA
authors.lastname: Farr
authors.forename: H J
authors.initials: HJ
authors.lastname: Steinfelder
authors.forename: S
authors.initials: S
authors.lastname: Radovick
authors.forename: N
authors.initials: N
authors.lastname: Gesundheit
authors.forename: P W
authors.initials: PW
authors.lastname: Gyves
authors.forename: T
authors.initials: T
authors.lastname: Taylor
authors.forename: G S
authors.initials: GS
authors.lastname: DeCherney
mesh_terms: D006801:Humans; D014176:Protein Biosynthesis; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013972:Thyrotropin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D013972:Thyrotropin