Effects of Interferons on Cortisol Production in Bovine Adrenal Fasciculata Cells Stimulated by Adrenocorticotropin

Author:

Tachikawa Eiichi1,Itho Koji1,Kudo Kenzo1,Harada Kazuho1,Kashimoto Takeshi1,Hirota Yoshikazu2

Affiliation:

1. Department of Pharmacology, School of Medicine, Iwate Medical University, Uchimaru 19-1, Morioka 020-8505, Japan

2. Department of Immunology, National Institute of Animal Health, 3-1-1, Kannondai, Tsukuba, Ibaraki 305-0856, Japan

Abstract

Abstract The effects of interferons (IFNs) IFN-α, IFN-β and IFN-γ on the production of cortisol in bovine adrenal fasciculata cells have been investigated. Pretreatment of the fasciculata cells with recombinant interferon-α-2b from man (over 300 units mL−1), but not with fibroblast IFN-β or recombinant IFN-γ from man, reduced the production of cortisol in cells stimulated with adrenocorticotropin (ACTH) (1 nM). IFN-α-2b inhibited ACTH-induced cortisol production in a concentration- (300-15 000 units mL−1) and time- (2–24 h) dependent manner. The inhibitory effect of IFN-α-2b on the production was abolished when the cells were simultaneously treated with anti-IFN-α antibody, and it was reversible. IFN-α-2b also inhibited dibutyryl cyclic AMP-induced production of cortisol but not pregnenolone-induced production. The effect of IFN-α-2b was not influenced by increases in external ACTH and Ca2+ concentrations and IFN-α-2b did not affect the ACTH-induced increase in cyclic AMP level in the cells. These results strongly suggest that IFN-α-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-α-2b for inhibition, and because of the ineffectiveness of IFN-β and IFN-γ.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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