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Hormonal effects on the regulation of hepatic heme biosynthesis

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Summary

Drug-induced porphyrin accumulation occurs in chick embryo liver cells maintained in serum-free Waymouth MD 705/1 medium. Addition of insulin and thyroxine to the medium results in a marked enhancement of porphyrin accumulation. The addition of hydrocortisone results in a further enhancement of porphyrin accumulation.

Several agents which are reported to increase intracellular adensosine 3′:5′-monophosphate (cAMP) levels, viz. glucagon, sodium fluoride, cAMP or its dibutyryl derivative, 3-isobutyl-1-methylxanthine and papaverine enhanced drug-induced porphyrin biosynthesis. On the other hand, agents which are reported to decrease intra-cellular cAMP levels, viz. alloxan and imidazole, diminished drug-induced porphyrin accumulation. cAMP appears to enhance, but not to function as a “second messenger” in drug-induced porphyrin biosynthesis.

Drug-induced porphyrin accumulation in chick embryo liver cells depend upon the insulin to glucagon ratio. A low level of porphyrin accumulation occurs at insulin to glucagon ratios similar to those found following glucose administration in vivo, suggesting a possible explanation for the therapeutic effect of glucose in hepatic porphyria.

The 5αH(A:B trans) and 5βH(A:B cis) steroids are equipotent in inducing δ-aminolevulinic acid synthetase and porphyrin accumulation in chick embryo liver cells maintained in serum-free culture medium. Thus, there is no specific steric requirement for porphyrin-inducing activity in steroids.

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Authors and Affiliations

  1. Department of Pharmacology, Queen's University, K7L 3N6, Kingston, Ontario, Canada

    G. S. Marks, J. K. Stephens, P. W. F. Fischer & R. O. Morgan

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  1. G. S. Marks
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  3. P. W. F. Fischer
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This work was supported by the Medical Research Council of Canada.

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Marks, G.S., Stephens, J.K., Fischer, P.W.F. et al. Hormonal effects on the regulation of hepatic heme biosynthesis. Mol Cell Biochem 25, 111–123 (1979). https://doi.org/10.1007/BF00228992

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