The Golgi apparatus and adrenal function: the effects of monensin on adrenocorticotropic hormone-stimulated steroidogenesis.
It has previously been shown that the steroidogenic action of adrenocorticotropic hormone (ACTH) is accompanied by characteristic alterations in cell ultrastructure. These include hypertrophy of the Golgi complex associated with increased vesicle formation and striking elevations of acid phosphatase activity in the Golgi complex and lysosomes. To investigate a possible relationship of these phenomena to steroidogenic function in monolayer cultures of murine adrenal tumor cells, monensin, a carboxylic ionophore which disrupts the ordered structure and transport function of the Golgi complex, was used. Monensin, at a concentration of 1.2 microM, causes massive vacuolization and hypertrophy of the Golgi complex. No effect on mitochondrial structure was seen. Monensin, 0.6-1.2 microM, inhibits both ACTH-stimulated and basal steroidogenesis by approximately 50% in incubations of 4 h or less. Dibutyryl-cAMP-stimulated steroidogenesis was inhibited to a similar degree. Incubations were carried out in serum-free media to eliminate possible effects due to exogenous cholesterol transport into the cell. There were no direct inhibitory effects of monensin on cholesterol side-chain cleavage (SCC) activity in isolated mitochondria. In contrast, mitochondria isolated from cells previously treated with monensin had a reduced capacity for this activity. These experiments suggest that monensin inhibits transport of cholesterol from the Golgi complex to the mitochondrial site of steroidogenesis action or interferes with the transport of key mitochondrial proteins synthesized on cytoplasmic ribosomes.
Cheng
B
B
Horst
I A
IA
Kowal
J
J
D000311:Adrenal Glands / Q000648:ultrastructure*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002784:Cholesterol / Q000096:biosynthesis; D005663:Furans / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects; D008985:Monensin / Q000494:pharmacology*; D011284:Pregnenolone / Q000096:biosynthesis; D013256:Steroids / Q000096:biosynthesis*
D005663:Furans; D013256:Steroids; D000643:Ammonium Chloride; D003994:Bucladesine; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D008985:Monensin; D002784:Cholesterol