Induction of Hepatic δ-Aminolevulinic Acid Synthetase by Oral Contraceptive Steroids

Abstract

The ability of oral contraceptive steroids to induce the hepatic enzyme, δ-aminolevulinic acid synthetase (ALAS), has been examined in vivo in a model test system utilizing 15- to 16-day-old chick embryos. ALAS controls the rate-limiting step in the biosynthesis of porphyrins and heme. All the progestational components of the contraceptive mixtures studied had potent ALAS inducing activity except for chlormadinone acetate. The inducing capacity of the different progestational agents varied, but all showed positive dose-response relationships. Neither of the estrogenic components of the oral contraceptives, mestranol or ethinyl estradiol, induced the enzyme significantly by itself, nor did these estrogens alter the degree of induction by the progestational compounds. The possible relevance of these findings to the increased urinary excretion of δ-aminolevulinic acid reported in some normal women receiving oral contraceptives, and to the experimental hormonal therapy of selected patients with acute intermittent porphyria, is discussed.