H. Homma et al., Estrogen suppresses transcription of lipoprotein lipase gene - Existence of a unique estrogen response element on the lipoprotein lipase promoter, J BIOL CHEM, 275(15), 2000, pp. 11404-11411
Estrogen exerts a variety of effects not only on female reproductive organs
but also on nonreproductive organs, including adipose tissue. Estrogen inh
ibits obesity triggered by ovariectomy in rodents. We studied the mechanism
underlying this estrogen-dependent inhibition of obesity. Estrogen markedl
y decreased the amounts of fat accumulation and lipoprotein lipase (LPL) mR
NA as well as triglyceride accumulation in genetically manipulated 3T3-L1 a
dipocytes stably expressing the estrogen receptor (ER), A pLPL(1980)-CAT co
nstruct, along with an ER expression vector, was introduced into differenti
ated 3T3-L1 cells, and CAT activities were determined, ER, mostly ligand-de
pendently, inhibited the basal LPL promoter activity by 7-fold. We searched
the LPL promoter for an estrogen-responsive suppressive element by employi
ng a set of 5'-deletion mutants of the pLPL-CAT reporter. Although there wa
s no classical estrogen response element, it was demonstrated that an AP-1-
like TGAATTC sequence located at (-1856/-1850) was responsible for the supp
ression of the LPL gene transcription by estrogen, An electrophoretic mobil
ity shift assay probed with the TGAATTC sequence demonstrated formation of
a specific DNA-nuclear protein complex. Interestingly, this complex was not
affected by the addition of any antibodies against ER, c-Jun, c-Fos, JunB,
or JunD, Because this TGAATTC element responded to phorbol ester and overe
xpression of CREB-binding protein abrogated the suppressive effect of estro
gen on the LPL promoter, we conclude that a unique protein that is related
to the AP-1 transcription factor families may be involved in the complex th
at binds to the TGAATTC element.