ESTRADIOL INHIBITS GROWTH-HORMONE RECEPTOR GENE-EXPRESSION IN RABBIT LIVER

We studied the ontogeny of GH receptor mRNA levels and the effect of e xogenous estradiol administration on GH receptor mRNA levels in rabbit liver. A solution hybridization-RNase protection assay revealed a pre dominant 370-base long protected band corresponding to the mRNA encodi ng the transmembrane GH receptor, and a 241-base long protected band, representing about 9.0%, with the predicted size for the truncated for m of the GH receptor. To study the developmental profile of GH recepto r expression, we studied 12 female rabbits, at ages 1, 3, 5 and 7 mont hs. Maximal GH receptor mRNA levels were observed in 3-month-old anima ls and decreased in 7-month-old animals. To investigate the effect of estradiol, 8-week-old immature female rabbits were randomly divided in to five groups, and received subcutaneous pellets containing either pl acebo or estradiol at doses of 0.1, 0.5, 1.5 and 5.0 mg for 3 weeks. E xogenous administration of estradiol, at doses that resulted in physio logical circulating levels, induced a reduction in GH receptor express ion, measured both by GH binding (36 and 46%), and GH receptor mRNA le vels (38 and 87%), in animals receiving pellets containing 1.5 and 5.0 mg of estradiol, respectively. We conclude that estradiol decreases G H receptor expression in rabbit liver. The results of our study sugges t that there is an inverse relationship between circulating estrogen c oncentrations and liver GH receptor expression.