Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors.
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function.
Barney
M
M
Department of Zoology and Neural Science Center, Brigham Young University, Provo, UT 84602, USA.
Call
G B
GB
McIlmoil
C J
CJ
Husein
O F
OF
Adams
A
A
Balls
A G
AG
Oliveira
G K
GK
Miner
E C
EC
Richards
T A
TA
Crawford
B K
BK
Heckmann
R A
RA
Bell
J D
JD
Judd
A M
AM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006854:Hydrocortisone / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D015383:Zona Fasciculata / Q000737:chemistry / Q000378:metabolism*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D000324:Adrenocorticotropic Hormone; D000262:Adenylyl Cyclases; D006854:Hydrocortisone