Pre-translational and post-translational regulation of TSH: relationship to bioactivity.
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 acetyl transferase 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. 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.
Weintraub
B D
BD
MCNEB, NIDDK, National Institutes of Health, Bethesda, Maryland.
Wondisford
F E
FE
Farr
E A
EA
Steinfelder
H J
HJ
Radovick
S
S
Gesundheit
N
N
Gyves
P W
PW
Taylor
T
T
DeCherney
G S
GS
D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes / Q000187:drug effects; D005809:Genes, Regulator; D006801:Humans; D011499:Protein Processing, Post-Translational; D013972:Thyrotropin / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
D005576:Colforsin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin