Further characterization of the inhibitory effect of monensin on adrenal steroidogenesis.
We have previously reported that treatment of cultured mouse adrenal tumor cells with 0.6-1.2 microM monensin, a monovalent carboxylic ionophore, results in disruption of the organized structure of the Golgi complex. This is associated with an inhibition of adrenocorticotropic hormone (ACTH) or dibutyryl cAMP-stimulated steroidogenesis and impairment of mitochondrial cholesterol side-chain cleavage activity. The present report describes further investigations regarding possible mechanisms for the inhibition. Monensin inhibits both synthesis of fluorogenic steroids and incorporation of [14C]acetate into the end-product steroid 11 beta,20 alpha-dihydroxy-4-pregnen-3-one. Supplementation of monensin-treated cells with 25-hydroxycholesterol, a readily available substrate for steroidogenesis, does not reverse the inhibitory effect on the reaction. The incorporation of L-[35S]methionine into trichloroacetic acid precipitable proteins in the isolated mitochondria of monensin-treated cells is inhibited approximately by 40%, whereas the inhibitory effect on the proteins in the cell homogenate is marginal. These findings suggest that a deficiency of newly synthesized proteins in mitochondria, rather than the availability of the substrate cholesterol, may be the primary factor causing impairment of steroidogenesis.
Cheng
B
B
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Horst
I A
IA
Kowal
J
J
D000085:Acetates / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013256:Steroids / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000085:Acetates; D009363:Neoplasm Proteins; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D008985:Monensin; D008715:Methionine