Heme oxygenase-2 mRNA: developmental expression in the rat liver and response to cobalt chloride.

We have previously identified two isozymes of heme oxygenase, HO-1 and HO-2, in the rat liver exhibiting vastly different molecular biochemical properties, including their responses to various chemical inducers. In the present study of the livers of fetal and newborn rats (-1 day to 21 days) we observed marked differences in the developmental pattern of expression of the transcripts for the two forms of heme oxygenase. In addition, the transcripts for HO-1 and HO-2 vary in their number and response to treatment with cobalt chloride. Specifically, using a full length cDNA probe for HO-2, we observed the 1.3-kb mRNA previously shown to encode HO-2 in the testis, as well as a second less abundant transcript of 1.9 kb. An HO-1 cDNA probe detected only the anticipated single transcript of 1.8 kb. The abundance of each HO-2 homologous transcript was unaffected by cobalt chloride treatment (4 or 24 h) in newborn (7 days old) and adult rats. The 1.8-kb HO-1 mRNA, however, was markedly increased in abundance in both age groups by this treatment. The 1.3-kb HO-2 mRNA level nearly doubled after parturition, but remained essentially unchanged during the first 2 weeks of life, and only modestly increased by age 21 days. At all stages of development, the relative abundance of the 1.3- and 1.9-kb transcripts remained unchanged. In the case of 1.8-kb HO-1 mRNA, the level of mRNA was relatively constant during the first week of life, but was substantially reduced by age 14 days, and was further decreased by age 21 days and in the adult animals. In adult rats, the abundance of the 1.3-kb HO-2 mRNA did not markedly increase over that detected in the course of the early postparturition developmental period. The data suggest that the abundance of the two HO-2 homologous transcripts is not readily subject to regulation by chemicals at any stage of development. The expression of HO-1, on the other hand, is subject to such regulation throughout life, and its high transcript abundance in newborn rats may well reflect availability of an endogenous inducer.