Hormonal effects on the regulation of hepatic heme biosynthesis.
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 porphyrine accumulation. Several agents which are reported to increase intracellular adenosine 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 have, 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 5 alpha A(A:B trans) and 5 beta H(A:Bcis) steroids are equipotent in inducing delta-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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis; D000502:Allylisopropylacetamide / Q000494:pharmacology; D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002642:Chick Embryo; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000627:therapeutic use; D006418:Heme / Q000096:biosynthesis; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007664:Ketosteroids / Q000494:pharmacology; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D011164:Porphyrias / Q000188:drug therapy; D011166:Porphyrins / Q000096:biosynthesis*; D011278:Pregnanes / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013963:Thyroid Hormones / Q000494:pharmacology
D000731:Androstanes; D006728:Hormones; D007328:Insulin; D007664:Ketosteroids; D011166:Porphyrins; D011278:Pregnanes; D013963:Thyroid Hormones; D000502:Allylisopropylacetamide; D006418:Heme; D003994:Bucladesine; D005934:Glucagon; D000242:Cyclic AMP; D000624:5-Aminolevulinate Synthetase; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine; D006854:Hydrocortisone