Effects of recombinant human interleukin-1 alpha, -1 beta, 2 and 6 on ACTH synthesis and release in the mouse pituitary tumour cell line AtT-20.
The effects of recombinant human interleukin (rhIL)-1 alpha, -1 beta, 2 and 6 on the release of ACTH from the ACTH-producing tumour cell line AtT-20 of the mouse were studied during relatively long periods of incubation. Levels of ACTH in the media, measured by radioimmunoassay, were increased by the addition of rhIL-1 alpha or -1 beta after latent periods of more than 4 h. RhIL-1 alpha and -1 beta were almost equally potent in this experiment and the minimum, half-maximum and maximum effective concentrations of both rhIL-1 alpha and -1 beta were about 0.1 pmol/l, 1-3 pmol/l and 10-100 pmol/l respectively. During incubation with rhIL-1 beta, immunoreactive ACTH levels and mRNA levels of the ACTH precursor pro-opiomelanocortin in cells also increased without apparent changes in the growth rate of the cells. Although the AtT-20 cells used in this study were quite insensitive to human/rat corticotrophin-releasing hormone (CRH), the cells showed a significant response to CRH after incubation with rhIL-1 beta. RhIL-6 showed similar effects to those of rhIL-1 beta on ACTH synthesis and release; increasing ACTH in cells and media after a certain latent period. On the other hand, rhIL-2 did not change ACTH levels in the AtT-20 cells in this study. These observations indicate that rhIL-1 alpha, -1 beta and rhIL-6 have direct effects on ACTH-producing cells to stimulate the release and synthesis of ACTH after a latent period.
Fukata
J
J
Department of Internal Medicine, Kyoto University, Faculty of Medicine, Japan.
Usui
T
T
Naitoh
Y
Y
Nakai
Y
Y
Imura
H
H
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone