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The inhibition of human adrenal steroidogenic enzyme activities by suramin. 1989

H Ashby, and M DiMattina, and W M Linehan, and C N Robertson, and J T Queenan, and B D Albertson
Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, D.C. 20007.

Suramin has recently been used to treat patients with acquired immune deficiency syndrome because of the action of this drug on reverse transcriptase. Patients so treated developed the symptoms and hormonal profiles of adrenal insufficiency. To evaluate the mechanism of action of suramin on adrenalcortical function, adrenal mitochondrial and microsomal preparations from five subjects were assayed for steroidogenic enzyme activity in the presence and absence of suramin. Specifically, 3 beta-hydroxysteroid dehydrogenase/isomerase, 17 alpha-hydroxylase, 21-hydroxylase, 11 beta-hydroxylase, and 17,20-desmolase activities were measured in the presence of 0-5000 mumol/L suramin concentrations. In all assays, enzyme activities decreased in a dose-dependent fashion as suramin concentrations increased. The drug doses (calculated) that caused 50% inhibition of enzyme activity were: 21-hydroxylase activity, 50 mumol/L; 17 alpha-hydroxylase activity, 25 mumol/L; 17,20-desmolase activity, 50 mumol/L; 11 beta-hydroxylase, 2 mumol/L, and 3 beta-hydroxysteroid dehydrogenase/isomerase, 1200 mumol/L. These results suggest that suramin has a concentration-dependent inhibitory effect on the key P-450-regulated enzymatic steps in adrenal glucocorticoid steroidogenesis, which may explain the development of adrenal insufficiency in acquired immune deficiency syndrome patients treated with suramin.

UI MeSH Term Description Entries
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006913 Hydroxysteroid Dehydrogenases Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-. Hydroxysteroid Dehydrogenase,Dehydrogenase, Hydroxysteroid,Dehydrogenases, Hydroxysteroid
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000302 Adrenal Cortex The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN. Cortex, Adrenal
D013250 Steroid Hydroxylases Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism. Steroid Hydroxylase,Steroid Monooxygenases,Hydroxylase, Steroid,Hydroxylases, Steroid,Monooxygenases, Steroid
D013251 Steroid Isomerases Enzymes that catalyze the transposition of double bond(s) in a steroid molecule. EC 5.3.3. 3-Ketosteroid Isomerases,3-Oxosteroid Isomerases,3 Ketosteroid Isomerases,3 Oxosteroid Isomerases,Isomerases, 3-Ketosteroid,Isomerases, 3-Oxosteroid,Isomerases, Steroid
D013498 Suramin A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Germanin,Moranil,Naganin,Naganol,Naphuride,Suramin Sodium,Suramin, Hexasodium Salt,Suramin, Monosodium Salt,Hexasodium Salt Suramin,Monosodium Salt Suramin,Salt Suramin, Hexasodium,Salt Suramin, Monosodium,Sodium, Suramin
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse

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