The complete nucleotide sequence of porcine uteroferrin mRNA was determined by analysis of overlapping cDNA and genomic clones. The uteroferrin mRNA is 1,424 nucleotides in length and encodes a precursor protein of 338 amino acids, of which 20 residues subsequently are cleaved to form the mature peptide. The uteroferrin gene spans 3.5 kb and consists of three exons and two introns. The first intron separates the 5' untranslated sequences from the translation initiation codon ATG while the other intron interrupts the coding region of the mature protein. Primer extension analysis localized the presumptive transcription initiation site of the mRNA 94 nucleotides 5' of the ATG. No canonical TATA or CAAT sequences were apparent upstream from the mRNA cap site. However, sequences within the 5'-flanking region of the gene exhibit similarities to defined regulatory sequences for iron- and steroid hormone-responsive genes. The steady-state level of uteroferrin mRNA is enhanced by progesterone but not by estrogen alone, although the extent of progesterone induction is lower than at midgestation. The simple organization of the uteroferrin gene, which contrasts with those of the transferrin gene family, and the progesterone induction of uteroferrin mRNA expression suggest that, although this protein may have evolved in a manner distinct from other iron binding proteins, its regulation by steroid hormones may be similar.