Effects of interferons on cortisol production in bovine adrenal fasciculata cells stimulated by adrenocorticotropin.
The effects of interferons (IFNs) IFN-alpha, IFN-beta and IFN-gamma on the production of cortisol in bovine adrenal fasciculata cells have been investigated. Pretreatment of the fasciculata cells with recombinant interferon-alpha-2b from man (over 300 units mL(-1)), but not with fibroblast IFN-beta or recombinant IFN-gamma from man, reduced the production of cortisol in cells stimulated with adrenocorticotropin (ACTH) (1 nM). IFN-alpha-2b inhibited ACTH-induced cortisol production in a concentration- (300-15000 units mL(-1)) and time- (2-24h) dependent manner. The inhibitory effect of IFN-alpha-2b on the production was abolished when the cells were simultaneously treated with anti-IFN-alpha antibody, and it was reversible. IFN-alpha-2b also inhibited dibutyryl cyclic AMP-induced production of cortisol but not pregnenolone-induced production. The effect of IFN-alpha-2b was not influenced by increases in external ACTH and Ca2+ concentrations and IFN-alpha-2b did not affect the ACTH-induced increase in cyclic AMP level in the cells. These results strongly suggest that IFN-alpha-2b reduces ACTH-induced production of cortisol in bovine adrenal fasciculata cells by affecting the early process of cortisol synthesis. The results also indicate that IFNs might not directly affect steroidogenesis in the adrenal cortex in-vivo, because of the requirement of high concentrations of IFN-alpha-2b for inhibition, and because of the ineffectiveness of IFN-beta and IFN-gamma.
Tachikawa
E
E
Department of Pharmacology, School of Medicine, Iwate Medical University, Morioka, Japan.
Itho
K
K
Kudo
K
K
Harada
K
K
Kashimoto
T
T
Hirota
Y
Y
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D011284:Pregnenolone / Q000494:pharmacology; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D013997:Time Factors; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003994:Bucladesine; D011284:Pregnenolone; D016899:Interferon-beta; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D007372:Interferons; D002118:Calcium; D006854:Hydrocortisone