AMP-Activated Protein Kinase Inhibits the Expression of StAR and P450scc in the Bovine Adrenal Zona Reticularis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 358-380-Steroid Hormone Biosynthesis & Metabolism
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-363
Matharage Shenali Ireha De Silva*, Carl I Larkin, Lance R Rhoten, David J Hepworth, Nathaniel R Nelson, Logan W Thomas, John W Mallett and Allan M Judd
Brigham Young University, Provo, UT
AMP activated protein kinase (AMPK) is a major energy sensor in many cells.  In addition, AMPK mediates the effects of the cytokine interleukin-6 (IL-6) in some tissues. Previous studies performed in our laboratory demonstrated that IL-6 decreases bovine zona reticularis (ZR) adrenal androgen release and the expression of ZR steroidogenic proteins including StAR and P450scc.  These effects are mediated through an increase in the nuclear factor DAX-1 that inhibits steroidogenesis and a decrease in the nuclear factor SF-1 that stimulates steroidogenesis.  In this study, we investigated the role of AMPK in mediating the effects of IL-6 on adrenal ZR adrenal steroidogenesis.   Bovine adrenal glands were obtained from an abattoir and the ZR isolated by dissection.  Small cubes of this tissue were then incubated under an atmosphere of 95% oxygen; 5% carbon dioxide.  Incubation (1 h) with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (0.3 to 3 mM) in a concentration-dependent manner decreased StAR (36% of control at 3 mM AICAR), SF-1 (40% of control at 3 mM AICAR), and P450scc (47% of control at 3 mM AICAR) protein expression, and increased the expression of the DAX-1 (180% of control at 3 mM AICAR) protein. Likewise AICAR incubations between 30 to 180 min in a time dependent-manner decreased StAR, SF-1, P450scc protein expression and increased DAX-1 protein expression. The effects of AICAR are mediated by an increase in AMPK activity because AICAR increased the phosphorylation of the enzyme acetyl CoA carboxylase (240% of control at 1 h incubation with 3 mM AICAR), a common index of AMPK activation.   Furthermore, compound C, an AMPK inhibitor, attenuated the effects of AICAR on StAR, P450scc, SF-1, and DAX-1.  Because the effects of IL-6 on steroidogenic proteins are similar to AICAR, the role of AMPK in IL-6 effects on the ZR was investigated by utilizing compound C.  The IL-6-mediated decrease in the expression of StAR, SF-1, P450scc, and increase in DAX-1 were attenuated by co-incubation with compound C.  Thus, the inhibition of zona reticularis P450scc, StAR, and adrenal androgen release mediated by IL-6 may occur via the activation of the AMPK pathway and this activation may increase the expression of DAX-1 and decrease the expression of SF-1.

Nothing to Disclose: MSID, CIL, LRR, DJH, NRN, LWT, JWM, AMJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm