The GHR is essential for the actions of growth hormone on postnatal growth and metabolism. The control of the murine GHR gene expression is complex; at least two 5′-untranslated exons have been identified. These exons, named L1 and L2, are differentially expressed with L1 expression being maximum in the liver whereas L2 expression predominates in the placenta. In the liver, expression of GHR is increased dramatically (2-4 fold) during pregnancy. In transient transfection experiments, we previously identified and characterizedcis-acting elements regulating the expression of the L1 transcript(JBC 1995;270:8851 & Endocrinology1995;136:5236). To characterize further the functional role of these cis-elements in an in vivo model, we engineered mice carrying a 3.5 kb fragment of the L1 promoter as a fusion gene with the reporter protein luciferase. Three founder mice were obtained with the transgene integrated into the germ line. Analysis of expression of the transgene was carried out by RT-PCR. Whereas the expression of the L1 transgene was demonstrated at low levels in various tissues in both ♂ and♀ mice, pregnant mice had an upto 10 fold increase in liver mRNA compared to non-pregnant ♀ or ♂ mice. We conclude that (1) in pregnancy, the expression of the L2 transcript remains unchanged, whereas expression of the L1 transcript in the liver is upregulated and, (2) the identified 3.5 kb promoter region contains the cis-acting elements controlling this pregnancy-specific expression. We speculate that this selective upregulation of the L1 GHR transcript in the liver during pregnancy facilitates adaptation of maternal metabolism to pregnancy.