Steroids porphyria inducers

Rg. 5. A metabolic scheme of steroids and their relative porphyria-inducing abilities in chick embryo liver cells in culture. 

A number of diverse findings have elucidated the control mechanisms for heme in the liver cell. These findings had their origin in studies of hepatic porphyria—acute intermittent porphyria (AIP), a relatively rare disease of humans. They led to studies of drug-induced or chemical porphyria and to the more recent findings that certain steroids are active in the control of heme. 

The chemicals that induce hepatic porphyria in man, animals, or chick embryo cells in culture consist of a wide variety of organic compounds that differ in physiologic activity. They include, for example, the central nervous depressants such as the barbiturates, sulfonme-thanes, and glutethimides the anticonvulsant methsuximide the central nervous stimulant bemegride the fungicides griseofulvin and hexachlorobenzene some chlorinated insecticides and the isoprenoid terpenes and steroids [2,10,11,24,25]. 

The steroid class of compounds was studied intensively for the relation of structure to inducing function because, of all the inducing compounds known, only the steroids are derived from physiological sources [65,66]. In addition, certain clinical observations, reviewed by DeMatteis [2], suggested that during puberty, pregnancy, and menstruation—that is, when steroid production changed markedly—the symptoms of hepatic porphyria in patients with this disease were exacerbated or diminished. 

Primary adrenal and gonadal hormones as well as certain steroid components of contraceptive pills were found to have weak inducing activity in the chick embryo liver test [25,65]. In the hepatic porphyria patient even these weakly inducing steroids may be dangerous. 

The dominant Mendelian inheritance of acute intermittent porphyria is most simply explained as a defect in an operator gene that controls the operon for the synthesis of mRNA of ALA-synthetase. On the basis of this assumption, an operator-repressor mechanism at the transcriptional level is proposed (Fig. 8). Inducers like the 5p H steroid, etio-cholanolone, or chemicals like DDC would react with the repressor and derepress or unblock the operator. Then mRNA for ALA-synthetase could be made (Reaction 1). 

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