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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0377v1 199/3/435    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mikhaylova, I. V Articles by Voutilainen, R. PubMed PubMed Citation Articles by Mikhaylova, I. V Articles by Voutilainen, R.

Department of Pediatrics, Kuopio University and University Hospital, PO Box 1777, FI-70211 Kuopio, Finland¹ Institute of Biomedicine/Medical Biochemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland

(Correspondence should be addressed to R Voutilainen; Email: raimo.voutilainen{at}uku.fi)

Leukemia inhibitory factor (LIF) is a multiple function cytokine regulating the hypothalamic–pituitary–adrenal axis at the pituitary level. LIF and its receptor are expressed in the adrenal glands, suggesting their potential regulatory role also at the adrenal level. Our aim was to clarify the effects of LIF on adrenal steroidogenesis using cell culture conditions. NCI-H295R human adrenocortical cells were treated with LIF (0.01–100 ng/ml) for 3–48 h with or without 8-bromo-cAMP (8-Br-cAMP; 1 mM). LIF treatment augmented cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, and aldosterone production (up to 224, 211, 149, 229, and 170% of control respectively, P<0.05 for all). It increased basal steroidogenic acute regulatory protein (STAR) and 17-hydroxylase/17,20-lyase (CYP17A1) mRNAs (up to 142 and 170% of control respectively, P<0.05) and the respective proteins, but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) mRNA (down to 72% of control, P<0.05), and protein. LIF also increased 8-Br-cAMP-induced cortisol and DHEA production and STAR mRNA accumulation, while it attenuated 8-Br-cAMP-induced HSD3B2 expression and androstenedione production. It had an additive effect on tumour necrosis factor-induced cortisol production. LIF had no effect on apoptosis, but it increased slightly the number of metabolically active cells (up to 120% of control, P<0.05). These findings indicate that LIF is a potential physiological and/or pathophysiological regulator of steroidogenesis at the adrenal level.