Hormonally regulated mammalian gene expression: steady-state level and nucleotide sequence of rabbit uteroglobin mRNA

Uteroglobin is a protein that is synthesized in large quantities by the rabbit uterine endometrial cells and secreted into the uterine lumen around the time of implantation of the developing blastocysts. The protein is also synthesized constitutively at a low level in the lung. In the uterus, synthesis of the protein is induced by progesterone but repressed by estradiol; whereas in the lung, it is not hormonally responsive. Using a full-length cDNA clone, we have established the nucleotide sequence of uteroglobin mRNA and have determined its levels in uterus and lung during early pregnancy. The clone, pUG617, contains all but 24 nucleotides at the 5' untranslated region of the structural gene. To establish the full mRNA sequence, we isolated a 5' end-labeled DNA fragment from pUG617 and extended its length using reverse transcriptase after hybridization with uterine poly(A)-containing RNA. The 5'-terminal sequence of uteroglobin mRNA was established by sequencing the extended DNA fragment. The nucleotide sequence of the peptide-coding portion of the gene has resolved some previously reported discrepancies in the amino acid sequence of the mature protein and those in the signal peptide. By comparison of sequences with a partial uteroglobin cDNA clone isolated by another laboratory, a polymorphic nucleotide at position 246 of the gene has been identified, where a G-A transition has caused an amino acid substitution from aspartic acid to asparagine at residue 46 of the mature protein. Analysis of steady-state RNA levels in the uterus has shown that the induction and repression of uteroglobin synthesis during early pregnancy is the result of accumulation and depletion of its mRNA, respectively. During the same period in the lung, no consistent changes in uteroglobin mRNA level were evident, reflecting the constitutive levels of the protein in this tissue.