NOVEL REGULATION OF DELTA-AMINOLEVULINATE SYNTHASE IN THE RAT HARDERIAN-GLAND

The mode of expression of delta-aminolevulinate synthase (ALAS), as we ll as that of mRNAs for other heme pathway enzymes, was examined in th e rat Harderian gland. Northern blot and in situ hybridization analyse s demonstrated that the non-specific ALAS (ALAS-N) mRNA is highly expr essed in this tissue, whereas the erythroid-specific ALAS (ALAS-N) mRN A is not. Immunoblot analysis of ALAS also confirmed this finding at t he protein level. ALAS-N mRNA was maximally induced in the Harderian g land and was not increased further by treatment of animals with 2-ally l-2-isopropylacetamide (AIA). The levels of mRNAs for other heme pathw ay enzymes, i.e., delta-aminolevulinate dehydratase, porphobilinogen d eaminase, uroporphyrinogen decarboxylase, and coproporphyrinogen oxida se, also were increased markedly in the Harderian gland and not influe nced by AIA. treatment. The level of ferrochelatase (FeC) mRNA in the gland was, however, lower than that in the liver. The gland contained an extremely high level of protoporphyrin, while heme was undetectable . Microsomal heme oxygenase-1 (HO-1) mRNA levels were significantly hi gher in the Harderian gland than in the liver. When isolated glands we re incubated with hemin in vitro in organ cultures, the level of HO-1 mRNA was increased, whereas the ALAS-N mRNA level was not. These findi ngs indicate that markedly elevated levels of protoporphyrin and extre mely low levels of heme in the Harderian gland are the results of both decreased expression of FeC and markedly increased expression of ALAS -N and HO-1. The constitutive expression of the ALAS-N gene in the Har derian gland suggests a novel transcriptional control mechanism of thi s gene. (C) 1997 Elsevier Science Inc.