Direct effects of IL-15 on corticosterone secretion by rat adrenocortical cells.
Cytokines might regulate the function of the hypothalamic-pituitary-adrenal axis. IL-15 is a potent non-T-cell-derived cytokine with IL-2-like activities. It has been shown that IL-15 can reverse the inhibition of glucocorticoids on PBMC. In vitro experiments were designed to assess the direct effect of IL-15 on corticosterone (CORT) secretion in the adrenal zona fasciculata-reticularis (ZFR) cells of male rats. Administration of IL-15 dose dependently decreased the basal and adrenocorticotropin-stimulated release of CORT and production of cAMP in ZFR cells. The stimulatory effect of forskolin (an adenylate cyclase activator) on CORT secretion and accumulation of cAMP in ZFR cells was attenuated by the administration of IL-15. However, 8-Br-cAMP (a cAMP analogue)-stimulated release of CORT was not affected by IL-15. Exogenous administration of IL-15 (10(-7) mol/L) significantly attenuated the pregnenolone (the substrate of 3beta-hydroxysteroid dehydrogenase)- or deoxycorticosterone (the substrate of 11beta-hydroxylase)-induced release of CORT. The results indicate that decrease of CORT secretion by IL-15 is in part because of (i) the decrease of adenylate cyclase activity and cAMP production and (ii) the inhibition of 3beta-hydroxysteroid dehydrogenase and 11beta-hydroxylase activities in rat ZFR cells.
Lo
Ming-Jae
MJ
Department of Early Childhood Education, National Tai-Chung University, Taichung, Taiwan. mjlo@ms3.ntcu.edu.tw
Lee
Shin-Da
SD
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000302:Adrenal Cortex / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019409:Interleukin-15 / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D015383:Zona Fasciculata / Q000378:metabolism
D019409:Interleukin-15; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D013252:Steroid 11-beta-Hydroxylase; D000262:Adenylyl Cyclases; D003345:Corticosterone