Mechanism of repression of 11β-hydroxysteroid dehydrogenase type 1 by growth hormone in 3T3-L1 adipocytes

Endocrine Journal

Izumi Fukuda¹  Atsuhiro Ichihara¹  Yukiko Ishikawa¹  Naomi Hizuka¹  Toko Muraoka¹ 

[1] Department of Medicine II, Tokyo Women’s Medical University, Tokyo 162-8666, Japan

关键词: Growth hormone (GH);    Insulin-like growth factor-I (IGF-I);    11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1);    Hexose-6-phosphate dehydrogenase (H6PDH);    Adipocytes;   

DOI  :  10.1507/endocrj.EJ13-0528

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(15)11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an NADPH-dependent reductase that converts cortisone to cortisol in adipose tissue. We previously reported that GH and IGF-I decrease 11β-HSD1 activity and mRNA levels in adipocytes. Hexose-6-phosphate dehydrogenase (H6PDH) is involved in the production of NADPH, which is a coenzyme for 11β-HSD1.The aim of the present study was to clarify further the mechanism of repression of 11β-HSD1 activity by GH using linsitinib, an IGF-I receptor inhibitor.The suppression of 11β-HSD1 mRNA by IGF-I was attenuated in the presence of 1 μM linsitinib (17.2% vs. 53.3% of basal level, P<0.05). 11β-HSD1 mRNA levels in cells treated with GH in the presence of 1 μM linsitinib were not different from those in absence of linsitinib (35.9% vs. 33.9%).The increase in IGF-I mRNA levels with GH and 1 μM linsitinib was not different from that in the absence of linsitinib (359% vs. 347%). H6PDH mRNA levels were significantly decreased in cells treated with IGF-I for 8 and 24 h (55.6% and 33.7%, P<0.05).In the presence of 1 μM linsitinib, there was no repression of H6PDH mRNA (111.4%). H6PDH mRNA levels were significantly decreased in cells treated with GH in the absence of linsitinib for 24 h (55.9%, P<0.05), but not for 8 h (89.5%).The presence of 1 μM linsitinib also prevented repression of H6PDH mRNA by GH over 24 h (107.8%).These results suggest that GH directly represses 11β-HSD1 mRNA rather than acting via the IGF-I receptor, and that GH represses H6PDH through locally produced IGF-I.

【 授权许可】

Unknown