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(Received for publication, April 19, 1996)
From the Metabolic Research Unit, University of California,
San Francisco, California 94143-0540
High level, anterior pituitary-specific
expression of the rat growth hormone (rGH) promoter requires
cooperative actions of several different transcription factors.
Previously, we described a series of multisubunit, tissue-general,
transcription factor complexes that bound to the GHF3 activation site
and strongly regulated rGH promoter activity. A 43-kDa DNA-binding
subunit common to each of the different GHF3 complexes is identified
here as the transcription factor, CCAAT/Enhancer-binding Protein
Volume 271, Number 35,
Issue of August 30, 1996
pp. 21484-21489
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Activation of the Rat Growth
Hormone Promoter in Pituitary Progenitor GHFT1-5 Cells
(C/EBP). In human monocyte U937 cells, which do not express the
endogenous or transfected GH genes, co-expression of C/EBP and Pit-1
synergistically activated the transfected rGH promoter. Full-length
C/EBP was present in the GH-secreting GC, and prolactin-secreting
235-1, pituitary cell lines, but not in GHFT1-5 cells, which are
transformed at a stage in development immediately prior to GH
expression. Transient expression of C/EBP in GHFT1-5 cells strongly
activated the co-transfected rGH promoter through the GHF3 binding
site; a second activation site mapped to evolutionary conserved GH
promoter sequences between 
106 and 33. C/EBP activation was
synergistic with phorbol 12-myristate 13-acetate and forskolin,
activators of protein kinases C and A, respectively. Thus, C/EBP is
an important regulator of rGH promoter activity that appears to
function in synergy with Pit-1, activators of A and C protein kinases
and possibly other factors.
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